sign in sign up
<<
Home , Asoxime chloride, Bithionol, Clobenpropit, Clocortolone pivalate, Dienestrol diacetate, Eicosanoid receptor

SUPPORTING INFORMATION SECTION

Drug Effects Viewed From a Signal Transduction Network Perspective

Anton F. Fliri,†,‡ William T. Loging§ and Robert A. Volkmann*,†,‡

† Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. ‡SystaMedic Inc.,1084 Shennecossett Road, Groton, CT 06340, USA. §Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.

TABLE OF CONTENTS

1320 Medicines Used in This Investigation……………………………………………S2

1179 (Accession Numbers) used for generating the co-investigation frequency spectra………………………………………………………………………………….S33

1082 COSTART terms…………………………………………………………………S60

Proteins (Accession Numbers) in network fragments I-IX…………………………….S83

Supplementary Tables 1& 2……………………………………………………………S99

Network Fragments I-IX………………………………………………………………S100

S1

Supplementary Figure 1: 1320 medicines

COMP_NAME monohydrate Betamethasone-21-Valerate Fludrocortisone Flumethasone Pivalate Acetate 6Beta-Hydroxycortisol Beclomethasone Dipropionate Propionate Pivalate Propionate Furoate etabonate Acetonide Flurandrenolide Acetonide 1,3,5(10)-Estratrien-3,17Beta-Diol-6-One 4-Hydroxyestrone 2-Hydroxyestradiol 2-Hydroxyestriol 4-Hydroxyestradiol 1,3,5(10)-Estratrien-2,3-Diol-17-One 2-Methyl Ether 2-Methoxyestradiol Beta- 3-Methyl Ether Ethinyl Estradiol 17Beta-Estradiol 17-Hemisuccinate Podocarpic Acid S2

Androstanolone Dehydrocholic Acid Ursodiol Terpin Hydrate Alprostadil Dinoprostone Allethrin Triacetin Loxoprofene Quinic Acid Succinic Anhydride Mupirocin Mycophenolate Mofetil HCl Pravastatin Artemether Artesunate PNU-0091638 Piperonyl Butoxide SC-41930 SC-53228 11-Beta,17-Alpha-Dihydroxypregn-4-Ene-3,20-Dione 17Alpha-Hydroxypregnenolone 4-Androsten-4-Ol-3,17-Dione 17Alpha-Hydroxyprogesterone 5-Cholesten-3Beta-Ol-7-One Calcifediol 19-Hydroxyandrost-4-Ene-3,17-Dione Uvaol 17 Alpha-Dihydroequilin

S3

Equilin Norethindrone Norethynodrel Acetate Ethynodiol Diacetate Acetate Acetate Medroxyprogesterone Acetate Acetate Acetate Desoxycorticosterone Pivalate Hydroxyprogesterone Caproate Testosterone Decanoate All-Trans-Retinol Phytonadione Ubidecarenone Clofibrate Ciprofibrate Bromopropylate Fenofibrate Deltamethrin Cyfluthrin Lambda-Cyhalothrin Fenpropathrin Fenvalerate 3,4 Dichlorophenol Chloroxylenol Bis(2-Hydroxy-5-Chlorophenyl) Bithionol Diflunisal 2-Amino-5-chlorobenzophenone HCl

S4

Dicofol Plifenate Lindane Indomethacin Cerivastatin Fluvastatin 1,5-Isoquinolinediol 5,7-Dichlorokynurenic Acid FPL 64176 Bisacodyl Papaverine HCl RG-13022 Ethacrynic Acid Butylparaben Ethylparaben Gemfibrozil Octyl Salicylate Ethyl 2-Cyano-3,3-Diphenylacrylate Phenothrin Monobenzone Citrinin Dehydroacetic Acid Dithianon 1,4-Benzoquinone Menadione Phenindione Benzoyl Peroxide Mandelic Acid Pyromellitic Acid

S5

2-Tert-Butyl-4-Hydroxyanisole 3-tert-Butyl-4-hydroxyanisole Guaiacol Propofol Probucol 2,2'-Dihydroxy-4,4'-Dimethoxybenzophenone Oxybenzone Erbstatin Analog Sodium Methylparaben Diacerein Aloe- Emodin Butein Resorcinol Aurintricarboxylic Acid Trisalicylic Acid Amygdalin Trihydrate Arbutin Guaifenesin Aloin Mangiferin Aflatoxin B1 Aflatoxin G1 Etoposide Teniposide PD-0156707-0015 Podophyllotoxin Cromolyn Sodium Dicumarol Methoxsalen Gallocatechin Gallate, (-)-

S6

Gossypetin Hematein PCO 400 O-Cresolphthalein Bromadiolon Coumachlor Warfarin Phenprocoumon Amifostine CGP 35348 Alendronate Sodium Pamidronate Ibandronate sodium Carmustine Deferoxamine Mesylate Ifosfamide Busulphan Acamprosate Mesna Sodium 0155098-0000 Chlorpyriphos-Methyl Fenchlorphos Bromfenvinphos Fensulfothion Isomalathion Arsenic Trioxide Trichlorfon Fosfomycin Tromethamine L-690,330 Risedronate Sodium Clodronic acid disodium salt Tiludronate Disodium (N-Benzylthiocarbamoyl)-L-Cysteine, S-

S7

Acetylcysteine DL-Thiorphan Actarit Aminohippuric Acid o-Iodohippuric Acid Aspartame Related Compound A H-Glu-Tyr-OH H-Tyr-Tyr-OH Aspartame Epibestatin HCl Nateglinide 4-P-PDOT Acetaminophen Benzocaine Butamben Methyl Anthranilate Exalamide Mexiletine HCl 4-(N-[3-Chlorophenyl]-Carbamoyloxy)-2-Butynyltrimethylammonium Chloride Barban PF-02543547-00 Fenoxycarb Metaxalone Racecadotril Maleate Gabexate Mesylate Isethionate Baclofen Cetraxate HCl Trans-4-(Aminomethyl)-Cyclohexanecarboxylic Acid Aminocaproic Acid Aminolevulinic Acid HCl Vigabatrin Azelaic Acid Undecylenic Acid Chlorobutanol Hexylene Glycol Penicillamine

S8

Dimercaprol Sorbitol AM-580 Bezafibrate Diatrizoic Acid Diatrizoic Acid Related compound A Iothalamic Acid Sodium Iodipamide Ipodate Sodium Chloramphenicol Chloramphenicol Palmitate Iohexol Iopamidol Metrizamide L-701,252 Flumequine Pazufloxacin Ochratoxin A L-689,560 Rebamipide PD-0167868-0000 Statil Balsalazide Olsalazine Disodium AG 957 Tranilast PD 098,059 ST638 Colchicine Trimethylcolchicinic Acid HCl Oxytetracycline Novobiocin Levodopa Metyrosine Liothyronine

S9

Aminosalicylic Acid Mesalamine m-Aminophenol Levonordefrin L-Bitartrate HCl Tyrphostin 51 Tyrphostin A9 Tyrphostin AG 879 Capsazepine A-77636 HCl HCl Norapomorphine HBr, R(-)- , hydrochloride 2-Methyl-5-Hydroxytryptamine Maleate BW 723C86 HCl Oxitriptan 6-Chloromelatonin CP-099994-01 Primaquine Phosphate Maleate HCl HCl HCl Methoctramine TetraHCl HCl HCl HCl HCl HCl HCl Fumarate DiH2O UK-538348-40 HCl HCl HCl SC-39566A

S10

Capsaicin Dihydrocapsaicin Flecainide Acetate Rolipram Troxipide Anisomycin Isamoltane Hemifumarate Malonate HCl HCl Fumarate HCl HCl Sulfate CP-114271 BRL 37344 Sodium HBr UK-519218-02 Albuterol Sulfate Epinephrine L-Bitartrate HCl Isoproterenol HCl L-Bitartrate HCl HCl Suloctidil Amphotericin B Nystatin Mepartricin A Aclarubicin HCl Azithromycin Clarithromycin Josamycin Dirithromycin Roxithromycin

S11

Rapamycin 7,8-Dihydroneopterin Zanamivir Hydrate Amikacin Arbekacin Sulfate Kanamycin Sulfate Paromomycin Sulfate Tobramycin Netilmicin Sulfate Sisomicin Sulfate Streptomycin Sulfate Miglitol Glucosamine HCl Voglibose 1,1-Dimethyl Biguanide HCl Altretamine Auramine O HCl Pinacidil Diphenylthiocarbazone Acetate M-Iodobenzylguanidine Hemisulfate Salt Phenformin HCl 5-(N-Ethyl-N-Isopropyl)-Amiloride Amiloride HCl Phenamil Methanesulfonate Anilazine Irsogladine Maleate WY-14643 10, 11-Epoxy Carbamazepine Oxcarbazepine 3,4,4'-Trichlorocarbanilide Diflubenzuron HCl Phenacemide Acetohydroxamic Acid Hydroxyurea Ciclopirox Olamine 3-Amino-6-chloro-1-methyl-4-phenylcarbostyril Pirfenidone

S12

Fluridon Amrinone Milrinone Niacinamide Pyrazinamide N-Methyl-Beta-Carboline-3-Carboxamide TJU103 Amlexanox Alloxazine Pteroic Acid Parbendazole Leflunomide Isradipine NVP-ABE-171 5-Phenylhydantoin Pemoline 0119307-0015 PD-0136095-0002 Siguazodan Zardaverine CP-057915 Fluorouracil Carmofur Mustard Amobarbital Secobarbital Mephobarbital Primidone 5-Nitro-6,7-Dichloro-1,4-Dihydro-2,3- Flutamide Acenocoumarol 5,5'-Dithiobis(2-Nitrobenzoic Acid) 3,5-Dinitrocatechol Ro 41-0960 Nifuroxazide

S13

Nitrofurazone 1,1'-Trimethylenebis[4-(Hydroxyiminomethyl)Pyridinium Bromide Chloride 0151832-0042 NO-711 HCl Oxyphencyclimine HCl Furaltadone Nitrofurantoin Molsidomine Oxadixyl Etanidazole N-Benzyl-2-Nitro-1 H-Imidazole-1-Acetamide Ornidazole Secnidazole , 6-Nitro-, Maleate Maleate Salt Diethyl 1,4-Dihydro-2,6-Dimethyl-3,5-Pyridinedicarboxylate Lacidipine Methyl 2-(Phenylthio)Ethyl 1,4-Dihydro-2,4,6-Trimethylpyridine-3,5- Dicarboxylate HCl Nitrendipine HCl Flunitrazepam Nitrazepam Desalkylflurazepam 1-(2-Chlorophenyl)-N-Methyl-N-(1-Methylpropyl)-3-Isoquinolinecarboxamide Flurazepam HCl Lormetazepam Temazepam

S14

Clofazimine Quazepam Pyridaben 4-Hydroxy- 3-Methyl-6-(3-[Trifluoromethyl]Phenyl)-1,2,4-Triazolo-(4,3-B)Pyridazine CGS-15943 ODQ Alprazolam Triazolam Midazolam Fluconazole Flutriafol Voriconazole Lonidamine Oxiconazole Dacarbazine Antipyrine Ibudilast Zaleplon Sulfinpyrazone Bitertanol Triadimefon Triadimenol Ebselen Linopirdine Ezetimibe NS-1619 UK-471858 LY 225910 PD-0216948-0000 PD-0185718-0002 Bifonazole Etomidate HCl Pilocarpine Bisulfate

S15

Ticlopidine HCl MK-886 Clomethiazole HCl UK-387284-04 Ro 41-1049 HCl Imazalil Sertaconazole Nitrate Tioconazole Cefaclor Cefprozil Z-Isomer Cephradine Cefoxitin Cephalothin Sodium Cefdinir Cefixime Cefotaxime Sodium Cefpodoxime Proxetil Ceftriaxone Sodium E-Isomer Ceftazidime Pentahydrate Cefazolin Cefotiam HCl Cefoperazone Dihydrate Cefmetazole Moxalactam Disodium Sodium Amoxicillin Ampicillin Sodium Carbenicillin Monosodium Monohydrate Cyclacillin Methicillin Sodium Sodium Aztreonam E-isomer Mezlocillin Sodium Piperacillin Sodium Sulbactam 8-Bromoguanosine 3',5'-Cyclicmonophosphate 8-Chloroadenosine 3',5'-Cyclic-Monophosphate CP-608039 UK-080067

S16

(4-Nitrobenzyl)-6-Thioguanosine, S- 6-Methylmercaptopurine Riboside 6-Mercaptoguanosine 8-Mercaptoguanosine 2-Chloro- N6-Cyclopentyladenosine Cladribine N6-Cyclopentyladenosine 5'-N-Ethylcarboxamidoadenosine 2-Phenylaminoadenosine 3-Deazaadenosine Vidarabine N6-Benzyladenosine Aminonucleoside Xanthosine Mizoribine Ribavirin Citicoline Sodium Capecitabine Enocitabine 5-Fluorocytidine 5-Fluorouridine Gemcitabine HCl 5-Bromo-2'-Deoxycytidine Floxuridine 4-Thiouridine Azacytidine Lamivudine Zalcitabine 2',3',5'-Tri-O-Acetyluridine Doxifluridine Tegafur 5-Ethyl-2'-Deoxyuridine Stavudine Zidovudine Related Compound B Zidovudine Abacavir Sulfate Olomoucine Acyclovir Penciclovir Adefovir Dipivoxil Famciclovir CE-308034 Tenofovir

S17

Amprolium HCl Pyrithiamine HBr Hydroxychloroquine Sulfate Monophosphate Chloride DiH20 Thiochrome Ajmaline CJ-023487-01 PD 123,319 Ditrifluoroacetate Benomyl Ro 15-4513 Apazone 3-Isobutyl-1-Methylxanthine Temozolomide Doxofylline Dyphylline Xanthinol Nicotinate UK-321130-16 CP-671906-01 Maleate Olmesartan Irbesartan Valsartan HCl PD-0132301-0002 Disopyramide Phosphate Isopropamide Iodide SC-40230 Imatinib Mesylate Citrate PF-03281206-01 Citrate Hydrogen Maleate Bupivacaine HCl Ropivacaine Mepivacaine HCl HCl Ergonovine Maleate Methylergonovine Maleate

S18

Methysergide Maleate Bepridil HCl HBr Eburnamonine, (-)- Vinpocetine LY-53,857 Maleate PF-00224440-00 5-Methoxy-N,N-Dimethyltryptamine Benzoate HCl Erythro-9-(2-Hydroxy-3-Nonyl) HCl N6-Cyclopentyl-9-Methyladenine Methanesulfonate DiHCl Tetrindole Mesylate Cyanocobalamin Camptothecin Irinotecan HCl Diaziquone Mitomycin Fropenem Epalrestat EBPC Tetramethrin Ethotoin Mephenytoin Thalidomide Methsuximide Phensuximide Paramethadione Trimethadione Enalaprilat Lisinopril Enalapril Maleate Ramipril Levetiracetam Protirelin Pidotimod

S19

Cycloheximide Ethosuximide Finasteride Glutethimide m- Ciglitizone PD-0128042-0000 UK-073967 UK-079300 Paxilline Stanozolol WIN-51708 Cilazapril Benazepril Quinapril Atorvastatin Calcium Itriglumide Repaglinide Vincristine Sulfate Nelfinavir Saquinavir PD-0134308-0533 PD-0154075-0000 PNU-0290932 Raltitrexed Acetate Thiostrepton Pioglitazone Rosiglitazone Maleate Hydrate Tropicamide HCl Clindamycin Phosphate Cyclosporine BZM, S(-)- IBZM, S(-)- L-Tartrate, S(-)- HCl

S20

Bromocriptine Mesylate Ergotaminine Dihydroergocristine Methanesulfonate Mesylate Dactinomycin Rifabutin Rifampin Rifapentine AG-036170 5-Methyl- Urapidil Nifekalant Ciprofloxacin HCl Gatifloxacin Lomefloxacin HCl Sparfloxacin Fleroxacin Rufloxacin HCl Enoxacin Pipemidic Acid Piromidic Acid AMI-193 L-Tartrate UK-419376-51 HCl HCl HCl CP-093393-01 Praziquantel Related Compound A Praziquantel Related Compound B Praziquantel Related Compound C Pirenzepine DiHCl

S21

Telenzepine DiHCl Fipexide HCl ICI 204,448 HCl GR 89696 Fumarate Zopiclone Moricizine HCl BD 1008 DiHBr ICI-199,441 HCl PF-00318418-00 PD-0129290-0002 U-62066 Itraconazole Diltiazem HCl ARC 239 DiHCl BMY 7378 DiHCl SNC 121 WAY 100635 Maleate DiHCl lomerizine DiHCl PF-02314494-00 Metocurine Iodide Tubocurarine Chloride Hydrate HCl RS 23597-190 HCl RS 67333 HCl HCl Mesylate HCl HCl Gefitinib UK-052046-27 Tyrphostin AG 1517 Trequinsin HCl 1-(2-Methoxyphenyl) HCl HCl

S22

Minaprine DiHCl Levodropropizine Fumarate Hycanthone Mitoxantrone diHCl diHCl Ranolazine HCl Quin 2 PD-0196860-0000 PF-01272315-00 PD-0172760-0000 Y-25130 HCl HCl Hemifumarate SC-51089 SC-51322 HCl Dihydrocodeine L-Bitartrate Hydrocodone L-Bitartrate HBr Codeine Sulfate Morphine Sulfate Pentahydrate Butorphanol L-Tartrate BNTX Maleate Nalbuphine HCl Naltrindole HCl Alcuronium Chloride L-741,626 HCl 3-Tropanyl-Indole-3-Carboxylate HCl Benztropine Mesylate 3-Tropanyl-3,5-Dichlorobenzoate Tropine 2-(4-Chlorophenoxy)Butanoate, Maleate HCl Sodium Sulfate Ipratropium Bromide HCl

S23

Homatropine Methylbromide Methscopolamine Bromide Scopolamine HBr Nalidixic Acid Cinoxacin GYKI 52466 HCl Bicuculline methbromide, 1(S), 9(R), (-)- Chloride Sanguinarine Chloride HCl SKF-96365 HCl BP 554 Maleate UK-076654-42 Mycophenolate Mofetil HCl Cinchonine Sulfate Sulfate Quininone Mesylate Tromethamine HCl Clidinium Bromide Mepenzolate Bromide 3-Quinuclidinyl Benzilate Trospium chloride Hemicholinium-3 HBr Glycopyrrolate Poldine Methylsulfate Amiprilose HCl HCl Gallamine Triethiodide Propantheline Bromide Pancuronium Bromide Carbetapentane Citrate Dicyclomine HCl

S24

Meperidine HCl PRE-084 HCl Oxybutynin HCl Oxyphenonium Bromide Tiamulin Fumarate HBr L-Tartrate Levallorphan L-Tartrate Meptazinol HCl Cephaeline HBr Benproperine Phosphate Tartrate HCl Propylnorapomorphine HCl, R(-)- Tolterodine L-Tartrate HCl Verapamil HCl YS 035 HCl Amorolfine HCl Levopropoxyphene Napsylate Succinate HCl Citrate HCl Eperisone HCl Tolperisone hydrochloride Dyclonine HCl Pramoxine HCl Centrophenoxine Clorgyline HCl SC-57461A HCl HCl Halofantrine HCl Hexahydro-Sila-Difenidol HCl, P-Fluoro Analog HCl HCl Procyclidine HCl HCl HCl

S25

Olopatadine hydrochloride Clomiphene Citrate Clomiphene Related Compound A CP-166221 Citrate Citrate Alverine Citrate Salt Mechlorethamine HCl Bromhexine HCl HCl Tosylate Chloride Naftifine HCl HCl Terbinafine HCl Thiobencarb Bethanechol Chloride Carbachol Chloride Acetylcarnitine HCl Levocarnitine Chloride Methacholine Chloride Succinylcholine Chloride HCl HCl Camostat Mesylate PD-0154117-0137 Trimebutine Salicylate Bromide Chlorambucil Pentetic Acid Mebrofenin Sodium Eusolex 6007 Tetracaine HCl Chloroprocaine HCl

S26

Procaine HCl Proparacaine HCl SDZ-205, 557 HCl Lidocaine Denatonium Benzoate QX-314 Crotamiton Prilocaine HCl Tocainide HCl N-Acetylprocainamide Procainamide HCl Succinate CGS-12066A Maleate CP-709877 PAPP 1-(3-Chlorophenyl)Piperazine HCl Quipazine Dimaleate L-745,870 TriHCl diHCl HCl HCl HCl GBR 12783 DiHCl GBR 12909 DiHCl GBR 13069 DiHCl Cis(Z)- DiHCl HCl Propericyazine 1,1-Dimethyl-4-Phenyl-Piperazinium Iodide Diphemanil Methylsulfate Decamethonium Bromide Pentolinium Bi-L-Tartrate Oxotremorine Methiodide Maleate HCl

S27

Pizotifen Malate HCl Metaphit Methanesulfonate HCl Bi-l-Tartrate DiH20 PD-0143188-6614 HCl Chlorpheniramine Maleate Maleate DiHCl Fumarate Pyrilamine Maleate HCl Imiquimod Maleate Pamoate Quinaldine Red HCl HCl Maleate HCl Methotrimeprazine Maleate HCl HCl Maleate HCl Trimeprazine Hemi-L-Tartrate Ethopropazine HCl HCl Methiothepin Mesylate Maleate HCl Anpirtoline Mefloquine HCl HCl Threo Isomer

S28

Perhexiline Maleate Salt CP-869342-00 DiHCl DiHCl Sulfate Trientine HCl Sulfate HCl HCl Iofetamine HCl Ethionamide Sulfate Salt HCl Mecamylamine HCl HCl HCl Iminodibenzyl HCl HCl Chloroethylclonidine DiHCl 2HBr HCl HCl Phosphate Mesylate Cibenzoline Succinate BU224 HCl HCl HCl HCl HCl N,N'-Bis[3-(4,5-Dihydro-1H-Imidazol-2-Yl)Phenyl]Urea Dipropanoate Hemifumarate PF-03253804-00 HCl HCl

S29

Trimethaphan Camsylate UK-456872 Riluzole Thiabendazole Thioguanine 1-Butyl-3-Sulfanilylurea Chlorpropamide Acetohexamide Glipizide Gliquidone Glyburide Amprenavir HCl HCl H-7 diHCl HA-1077 DiHCl ML-9 HCl H-9 DiHCl Monodansylcadaverine Crystalline malate CP-122288-42 Brinzolamide Dorzolamide Probenecid SB-269970 HCl Thiothixene Delavirdine Mesylate Vardenafil Citrate CP-820218 PNU-0101387G

S30

RS 67506 HCl SB-271046 hydrochloride Cyclopenthiazide Althiazide Benzthiazide Bendroflumethiazide Quinethazone Hydroflumethiazide Chlorothiazide Trichlormethiazide Metolazone Methyclothiazide Polythiazide PF-00596001-001 Clopamide Indapamide 4-Amino-6-chloro-1,3-benzenedisulfonamide Xipamide Folpet Chlorthalidone Saccharin 2-Hydroxysaclofen HCl PD-0166793-0000 4,4'-Diaminostilbene-2,2'-Disulfonic Acid Dapsone Suramine Sodium Salt 4-Formylbenzenesulfonamide Mafenide Acetate Sulfanilamide Sulfabenzamide Sulfacetamide Sulfanitran 2-Hydroxy-4-Methoxybenzophenone-5-Sulfonic Acid Phenolsulfonphthalein Ethoxzolamide

S31

Parecoxib Sodium Zonisamide Sulfaphenazole Acetazolamide Sulfamethizole Sulfathiazole Sulfamoxol Sulfisoxazole Torsemide Sulfadiazine Sulfamerazine Sulfamethazine Sulfisomidine Sulfapyridine Sulfaquinoxaline Sulfadoxine Sulfadimethoxine Sulfamonomethoxine Sulfamethoxypyridazine PD-0180988-0016 Rosuvastatin Ca Lansoprazole Pantoprazole Sodium Rabeprazole

S32

Supplementary Figure 2: 1179 Proteins (Accession Numbers) used for generating the co-investigation frequency spectra.

Target Name Accession 14-3-3gamma AB024334 15-hydroxy dehydrogenase J05594 2,3-oxidosqualene-lanosterol cyclase S81221 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase AF273765 3-oxo-5 alpha- 4-dehydrogenase 2 M74047 4-aminobutyrate aminotransferase (GABAT) U80226 4-hydroxyphenylpyruvate dioxygenase X72389 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase BC008879 5-hydroxytryptamine 1A (5HT1A) AB037529 5-hydroxytryptamine 1B receptor (5HT1B) AL049595 5-hydroxytryptamine 1D receptor (5HT1D) M89955 5-hydroxytryptamine 1E receptor (5HT1E) M92826 5-hydroxytryptamine 1F receptor (5HT1F) AB037533 5-hydroxytryptamine 2A receptor (5HT2A) X57830 5-hydroxytryptamine 2B receptor (5HT2B) X77307 5-hydroxytryptamine receptor (5HT2C) M81778 5-hydroxytryptamine 4 receptor (5HT4) Z48150 5-hydroxytryptamine 5A receptor (5HT5A) X81411 5-hydroxytryptamine 6 receptor (5HT6) L41147 5-hydroxytryptamine 7 receptor (5HT7) U68488 5-hydroxytryptamine receptor 3 subunit C(5HT3C) AF459285 5-methyltetrahydrofolate-homocysteinemethyltransferase U75743 5'-methylthioadenosine phosphorylase U22233 5-oxo-ETE receptor (TG1019) BC063549 6-O-methylguanine-DNA methyltransferase(MGMT) X54228 6PF-2-K/FRU-26-P2ase liver-type isozyme(includes 6- phosphofructo-2-kinase) AL049732 6-Phosphofructokinase C ( type) D25328 7-dehydrocholesterol reductase AF110060 a disintegrin and metalloproteinasedomain 17 (tumor necrosis factor, alpha, converting ) U92649 ABL kinase AJ131467 protein, alpha-6chain U62435 (ACHE) M55040 Acetyl-CoA carboxylase U19822 acid alpha-glucosidase preproprotein S76893 Acrosin Y00970 activin A receptor, type IB (ACVR1B) L31848 Activin receptor type I (ACTR-I / ALK-2) L02911 Activin receptor type II (ACTR-II) X62381 Activin receptor type IIB (ACTR-IIB) X77533 Activin receptor-like kinase 1 (ALK-1) U77713

S33

Acyl-CoA A: cholesterol acyltransferase 1(ACAT1) L21934 acyl-CoA synthetase long-chain family member 1 L09229 acyl-CoA synthetase short-chain family member 2 AF263614 ADAM-12 (meltrin alpha) AF023477 ADAMTS-4 (aggrecanase 1) AF148213 adaptor-associated kinase 1 (AAK1) AB028971 Adenine translocator 3 (ANT3) J03592 A1 receptor X68485 X68486 X68487 X76981 Adenosine deaminase (adenosineaminohydrolase) M13792 Adenosine kinase U50196 adenylate cyclase 5 U65473 Adenylate kinase 1 (AK1) J04809 precursor D45371 ADME: 1 L05500 ADP-ribosylation-like factor 6 interacting protein 5 BC005143 D43639 Adrenomedullin receptor (Y13583) Y13583 advanced glycosylation end product-specific receptor precursor agouti related protein homolog U89485 aminotransferase U70732 dehydrogenase beta-1-subunit(ADH1-2) L38290 Alcohol dehydrogenase class I gammasubunit (ADH3) X04299 aldo-keto reductase family 1, member A1 J04794 aldo-keto reductase family 1, member C1 M86609 Aldose reductase M59783 alpha 1,4-galactosyltransferase AB041418 Alpha mannosidase II D63998 Alpha platelet-derived growth factorreceptor (PDGF-R- alpha) M22734 Alpha-1A receptor D32201 Alpha-1-antitrypsin AF119873 Alpha-1B L31773 Alpha-1D adrenergic receptor S70782 alpha-1-fetoprotein transcription factor(LRH1) (NR5A2) AF124247 Alpha-2A adrenergic receptor M18415 Alpha-2B adrenergic receptor M34041 Alpha-2C-1 adrenergic receptor D13538 Alpha2Delta Calcium Channel AF042793 Alpha-2-plasmin inhibitor J02654 Alpha-amylase X07057 Alpha-L-fucosidase X01390 alpha-synuclein L36675 Alpha-tryptase (Tryptase 1) AF098328 Alpha- X06956 amine oxidase, containing 3 precursor AF054985

S34

Aminopeptidase A (Glutamylaminopeptidase) L14721 Aminopeptidase B AL390139 Aminopeptidase N (Microsomalaminopeptidase) AJ421875 AMPKa2 U06454 X13466 receptor L29496 Angiopoietin 1 receptor (TIE-2) (TEK) L06139 Angiotensin converting enzyme 2 (ACE2) AF241254 Angiotensin-converting enzyme 1 (ACE1) M26658 angiotensinogen preproprotein K02215 Aortic carboxypeptidase-like protein ACLP D86479 Apolipoprotein A AF158663 apolipoprotein B precursor X03325 Apolipoprotein E Z70760 Aquaporin 4 (AQP4) U34845 Arachidonate 12-lipoxygenase S68588 Arachidonate 15-lipoxygenase M23892 Arachidonate 5-lipoxygenase J04520 A-RAF Proto-oncogene /threonineprotein kinase U01337 vasopressin-neurophysin II preproprotein AF031475 Aromatic amino acid decarboxylase (ddc) L05075 ASIC2a Sodium channel(hBNaC2) U78180 Aspartate carbamoyltransferase (CAD) M38561 Aspartylglucosaminidase M64075 ATP citrate X64330 ATP-binding cassette transporter 1(ABCA1) AF165281 ATP-binding cassette, sub-family B(MDR/TAP), member 1 (ABCB1) (Multidrug resistance P-glycoprotein(MDR1) AF016535 ATP-binding cassette, sub-family G(WHITE), member 2 (ABCG2) (Breast cancer resistance protein) AF098951 ATP-sensitive inward rectifier potassiumchannel 1 (KIR 1.1) U12541 Aurora-related kinase 1 (ARK1) AF008551 Aurora-related kinase 2 (ARK2) AF015254 autocrine motility factor receptor M63175 AXL tyrosine protein kinase (UFO, GAS6receptor) X57019 B lymphocyte tyrosine kinase (BLK) S76617 B1 receptor (BK1) U12512 B2 (BK2) X86164 BACE (beta-secretase) (BACE1) AF200193 baculoviral IAP repeat-containing protein 4 U45880 basigin X64364 BCL1 (Cyclin D1) M64349 BCL2 M14745 BCL2-associated X protein AF008196 BCL2-interacting killer BC001599 BDNF/NT-3 growth factors receptor (TRK-B) S76473 Beta platelet-derived growth factorreceptor (PDGF-R-beta) J03278 Beta-1 adrenergic receptor J03019

S35

Beta-2 adrenergic receptor AF202305 Beta-3 adrenergic receptor X72861 Beta-adrenergic receptor kinase 1 (ARK-1)(GRK2) X61157 Beta-adrenergic receptor kinase 2 (ARK-2)(GRK3) X69117 beta-transducin repeat containing protein AF101784 Beta-tubulin X00734 receptor 3 (BRS-3) L08893 bone morphogenetic protein 1 (BMP1) M22488 bone morphogenetic protein 2 preproprotein AL035668 bone morphogenetic protein 7 precursor AL157414 Bone morphogenetic protein-4 type IIreceptor U25110 B-RAF Proto-oncogene (p94 kinase) M21001 branched chain aminotransferase 1, cytosolic U21551 Branched-chain alpha-keto aciddehydrogenase kinase AF026548 breast cancer 2, early onset X95152 Brutons tyrosine kinase (BTK) X58957 M16541 C3A anaphylatoxin chemotactic receptor(C3AR) U28488 C5A anaphylatoxin chemotactic receptor(C5AR) X57250 cadherin 16 precursor AF016272 cadherin 3, type 1 preproprotein X63629 Calcineurin B subunit isoform 1 (Proteinphosphatase 2B regulatory subunit) M30773 preproprotein Calcitonin -related type 1receptor U17473 (CT-R) L00587 calcitonin-related polypeptide, beta X04855 calcium channel, voltage-dependent, alpha 1I subunit (CACNA1I) (Cav3.3) AF211189 calcium channel, voltage-dependent, L type, alpha 1B subunit (CACNA1B) (Cav2.2) M94173 calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CACNA1A) (Cav2.1) U79663 Calcium/calmodulin-dependent proteinkinase II beta subunit (CAMK-II beta subunit) AF140350 Calcium-activated potassium channel Slo(MaxiK subunit) U11058 Calmodulin M19311 Calpain 1 X04366 Calpain 2 M23254 receptor 1 (CB1) X54937 2 (CB2) X74328 Carbonic anhydrase I M33987 carbonic anhydrase II X03251 carbonic anhydrase IV precursor L10955 carbonic anhydrase IX precursor X66839 carbonic anhydrase XII precursor carbonyl reductase 1 BC002511 carbonyl reductase 3 BC002812 Carboxypeptidase B2 (TAFI) AL137141

S36

Carcinoembryonic antigen CEA X16454 carcinoembryonic antigen-related cell adhesion molecule 5 M17303 Carnitine O-acetyltransferase (fragment) X78706 Carnitine palmitoyltransferase II M58581 Carnitine/acylcarnitine (CACT) Y10319 Casein kinase I delta (CKI-delta) U29171 Casein kinase I epsilon (CKI-epsilon) AL020993 Casein kinase II alpha chain (CK II) AL049761 Casein kinase II alpha prime chain (CKII) M55268 Caspase 1 (interleukin-1 beta convertase) U13697 Caspase 3 (apopain) U13737 Caspase 7 (ICE-like apoptotic protease 3) U67206 Caspase 8 AF102146 Caspase 9 (ICE-like apoptotic protease 6) AB019205 catalase AY028632 Catechol O-methyltransferase (COMT) Z26491 Cathepsin B (APP secretase) Y18460 Cathepsin D M11233 Cathepsin E AJ250716 Cathepsin G M16117 Cathepsin K U13665 Cathepsin L Y18462 Cathepsin S U07374 Z18951 caveolin 2 and b caveolin 3 AF036365 CCR1 L10918 CCR10 chemokine receptor U13667 CCR11 chemokine receptor AF110640 CCR2 chemokine receptor U80924 CCR3 chemokine receptor AF026535 CCR4 chemokine receptor X85740 CCR5 chemokine receptor AF011537 CCR6 chemokine receptor U68030 CCR7 chemokine receptor L31581 CCR8 chemokine receptor Y08456 CD14 antigen precursor X13334 CD164 antigen, sialomucin D14043 CD19 antigen M28170 CD1D antigen, d polypeptide M14664 CD2 antigen (p50), sheep red blood cell receptor M16336 CD22 antigen AB013007 CD25 Interleukin-2 Alpha (IL2) receptor M14098 CD28 antigen AF222341 CD33 antigen (gp67) M23197 CD34 antigen BC039146 CD36 antigen L06850 CD37 antigen X14046 S37

CD38 antigen D84276 CD4 antigen (p55) S79267 CD40 antigen precursor CD40 D31797 CD44 antigen precursor CD52 antigen X67699 CD59 antigen p18-20 X16447 CD6 antigen X60992 CD72 antigen M54992 CD74 antigen K01144 CD80 antigen (CD28 antigen ligand 1, B7-1 antigen) BC042665 CD83 antigen (activated B lymphocytes, immunoglobulin superfamily) AL022396 CD86 antigen U04343 CDC7-related kinase AB003698 CDK2-associated dual specificity proteinphosphatase L25876 cell division cycle 2-like 2 (CDC2L2) AF067515 C-FOS AF111167 chaperonin M34664 Checkpoint kinase (CHK2) AF086904 Checkpoint kinase CHK1 AF016582 Chemokine CCL2 (MCP1/MCAF) S71513 Chemokine CCL26 (Eotaxin3/IMAC) AF096296 Chemokine CX3C (fractalkine/neurotactin) AC004382 Chemokine CXCL1 (GROa/MGSAa) Chemokine CXCL12 (SDF-1) U16752 Chemokine CXCL8 (IL8) Z11686 chloride channel, calcium activated,family member 1 AF039400 preproprotein L00354 Cholecystokinin type A receptor (CCKA) L19315 Cholecystokinin type B receptor (CCKB) D13305 Cholesterol esterase M54994 Cholesteryl ester transfer protein M83573 O-acetyltransferase S56138 Choline/ethanolaminephosphotransferase(CEPT1) AF138862 Chymase ( protease I) S61334 ciliary neurotrophic factor S72921 Class I alcohol dehydrogenase (ADH1)alpha subunit M12271 class II alcohol dehydrogenase 4 pi subunit M15943 class IV alcohol dehydrogenase 7 mu or sigma subunit X76342 C-MAF (short form) AF055376 factor II (Prothrombin) M33031 coagulation factor III precursor M16553 Coagulation factor IX (Christmas factor) K02053 Coagulation Factor Protein C AB083690 Coagulation factor VII (Eptacog alfa) M13232 coagulation factor VIII isoform bprecursor K01740 Coagulation factor X (Stuart factor) M57285

S38

Coagulation factor XI (Plasmathromboplastin antecedent) AB004057 Coagulation factor XII (Hageman factor) L43615 Cold and Menthol Receptor (CMR1) BC001135 colony stimulating factor 1 precursor colony stimulating factor 2 precursor M11220 colony stimulating factor 2 receptor,alpha, low-affinity (granulocyte-macrophage) L29349 colony stimulating factor 3 precursor Complement C1R component X04701 Complement C2 (C3/C5 convertase) X04481 complement component 3 precursor K02765 complement component 5 S79279 Complement factor I (C3B/C4B inactivator) J02770 connective tissue growth factor X78947 Corticotropin releasing factor receptor 1(CRF1) U16273 Corticotropin releasing factor receptor 2(CRF2) AC004976 corticotropin releasing binding protein X58022 cRAF kinase X03484 C-reactive protein, pentraxin-related X56692 Creatine kinase M chain M14780 CRTH2 (GPR44) AF144308 CSK tyrosine kinase X60114 Cu/Zn superoxide dismutase (SOD,cytoplasmic) L46374 cubilin AF243082 CX3CR1 receptor U28934 CXCR1 chemokine receptor L19592 CXCR2 chemokine receptor M73969 CXCR3 chemokine receptor U32674 CXCR4 chemokine receptor Y14739 CXCR5 [ receptor for CXCL13 (BLCC/BCA-1)] X68149 Cyclin-dependent kinase 1 (CDK1) X05360 Cyclin-dependent kinase 2 (CDK2) X62071 Cyclin-dependent kinase 3 (CDK3) X66357 Cyclin-dependent kinase 4 (CDK4) U79269 Cyclin-dependent kinase 5 (CDK5) X66364 Cyclin-dependent kinase 8 (CDK8) X85753 cyclin-dependent kinase inhibitor 1B AF213700 Cyclooxygenase 1 (prostaglandinendoperoxide synthase 1) S36219 Cyclooxygenase 2 (prostaglandinendoperoxide synthase 2) M90100 Cysteinyl receptor (CYSLT1) AF119711 Cysteinyl (CysLT2) AB038269 Cystic fibrosis transmembrane conductanceregulator (CFTR) AC000061 deaminase AF095644 Cytochrome P450 11B1 (CYPXIB1) (steroid11-beta- hydroxylase) M24667 Cytochrome P450 11B2 (CYPXIB2) (steroid18-hydroxylase/ synthase) S77409

S39

Cytochrome P450 19 (CYPXIX / aromatase /oestrogen synthetase) Y07508 Cytochrome P450 1A2 (P-3-450) Cytochrome P450 21 (steroid21-hydroxylase) X58899 Cytochrome P450 27B (25-hydroxyvitaminD-1-alpha- hydroxylase) AB005038 Cytochrome P450 2B6 M29874 Cytochrome P450 2C19 (S-mephenytoin4-hydroxylase) M61854 Cytochrome P450 2C9 (CYP2C9) M21939 Cytochrome P450 2D6 (debrisoquine4-hydroxylase) M24499 Cytochrome P450 2E1 (-inducible) J02843 Cytochrome P450 2F1 J02906 Cytochrome P450 3A4 J04449 Cytochrome P450 3A5 (niphedipine oxidase) J04813 Cytochrome P450 51 (lanosterol14-alpha-demethylase) U51692 Cytochrome P450 5A1 (thromboxanesynthase) BC041157 Cytochrome P450 8A1 (prostacyclinsynthase) D84124 cytochrome P450, family 2, subfamily J,polypeptide 2 AF144566 Cytosolic phospholipase A2 AL049797 D(1A) receptor X55760 D(1B) M67439 D(2) dopamine receptor S69899 D(3) dopamine receptor U32499 D(4) dopamine receptor L12398 decay accelerating factor for complement (CD55, Cromer blood group system) S72858 Delta-type receptor (DOR-1) AL009181 Deoxycytidine kinase (DCK) M60527 deoxyhypusine synthase U26266 diablo precursor Diacylglycerol kinase alpha (DAG kinasealpha) AF064771 Diacylglycerol O-acyltransferase (DGAT) AF059202 Dihydrofolic acid reductase (DHFR) V00507 Dihydroorotate dehydrogenase M94065 Dihydropyridine-sensitive L-type calciumchannel alpha- 2/delta subunits AF083854 Dihydropyrimidine dehydrogenase AB003063 Dipeptidyl peptidase IV (DPP IV, CD26) X60708 dipeptidylpeptidase 7 AF154502 Dipeptidyl-peptidase I U79415 diphosphomevalonate decarboxylase U49260 disrupted in schizophrenia 1 AJ506177 DNAse I (DRNI) AC005203 Dopamine beta hydroxylase Y00096 Dual specificity protein phosphatase (MAPkinase phosphatase-5 / MKP-5) AF179212 Dual specificity protein phosphatase 3(VHR) L05147 Dual specificity protein phosphatase 8(HVH-5) U27193 Dual specificity protein phosphatase 9(MAP kinase U87167

S40

phosphatase-4/ MKP-4) Dual-specificitytyrosine-(Y)-phosphotylation regulated kinase (DYRK) AB015282 Dual-specificitytyrosine-(Y)-phosphotylation regulated kinase 2 (DYRK2) Y13493 dystrophin Dp140bc isoform M63072 E Selectin (Endothelial leukocyteadhesion molecule 1 / ELAM-1) M24736 E2F-1 (pRB-binding protein) X79444 ectonucleoside triphosphate diphosphohydrolase 1 U87967 ectonucleotide pyrophosphatase/phosphodiesterase 1 AJ242020 egl nine homolog 1 AF229245 empty spiracles homolog 1 X68879 endoglin precursor X72012 Endothelial lipase AF118767 Endothelial synthase (eNOS) D26607 endothelial protein C receptor precursor AL356652 1 Z98050 (ETB) L06623 Endothelin-1 receptor (ETA) S81542 Endothelin-converting enzyme 1 (ECE-1) X91923 eomesodermin AJ010280 Ephrin type-A receptor 2 (ECK) M59371 Ephrin type-B receptor 4 (HTK) U07695 epidermal growth factor (beta-urogastrone) X04571 Epidermal X00663 Epithelial discoidin domain receptor 1(CAK) U48705 epoxide 1, microsomal (xenobiotic) BC003567 epoxide hydrolase 2, cytoplasmic AF233336 ERBB-2 receptor protein tyrosine kinase(Tyrosine kinase- type HER2) M11767 ERBB-3 receptor protein tyrosine kinase(Tyrosine kinase- type cell surface receptor HER3) S61953 ERBB-4 receptor protein tyrosine kinase(Tyrosine kinase- type cell surface receptor HER4) L07868 ERK1 Z11696 erythropoietin precursor AF202311 M34986 receptor alpha (ER-alpha) AL049821 beta (ER-beta) AF074599 eukaryotic translation initiation factor2-alpha kinase 2 (EIF2AK2) M85294 Extracellular calcium-sensing receptor(CASR) S83176 Farnesol receptor HRR-1 U68233 Farnesyl pyrophosphate FPP synthetase J05262 Farnesyl-protein beta-subunit L10414 Fas-activated serine/threonine kinase(FAST) X86779 fatty acid amide hydrolase AF098019 fatty acid binding protein 4, adipocyte BC003672

S41

fatty acid desaturase 2 AF108658 fatty acid synthase U26644 F-box and WD-40 domain protein 1B AB014596 Fc fragment of IgE, low affinity II, receptor for (CD23A) X04772 Fc fragment of IgG, high affinity Ia, receptor (CD64) S45709 Fc fragment of IgG, low affinity IIIa, receptor for (CD16) AB025256 FGFR1 FGF receptor 1 X52833 -like 2 AF104015 Fibroblast activation protein (Seprase) U76833 fibroblast growth factor 10 precursor AB002097 fibroblast growth factor 16 AB009391 fibroblast growth factor 18 precursor AF211188 fibroblast growth factor 2 M17599 fibroblast growth factor 20 AB044277 fibroblast growth factor 21 precursor AB021975 fibroblast growth factor 3 precursor X14445 fibroblast growth factor 4 precursor J02986 fibroblast growth factor 5 precursor fibroblast growth factor 8 precursor fibroblast growth factor 9 precursor AL139378 Fibroblast growth factor receptor 2(FGFR-2) (Keratinocyte growth factor receptor) M97193 fibroblast growth factor receptor 3 precursor 1 preproprotein Five-lipoxygenase activating protein(FLAP) X52195 FKBP (12 FK-506) X55741 FKBP-rapamycin associated protein (FRAP,mTOR) L35478 FL receptor (FLT3) L36162 FMLP-related receptor I (FMLP-RI) D10922 FMLP-related receptor II (FMLP-R-II). M76673 Focal adhesion kinase 1 (FADK 1) L13616 Focal adhesion kinase 2 (FADK 2) S80542 Foetal liver kinase 1 (FLK-1)(geneseqp) Follicle stimulating (FSH-R) S59900 folylpolyglutamate synthase precursor fragile X mental retardation 1 BC038998 FRAP-related protein (FRP1) U49844 frequenin homolog X84048 10 transmembrane receptor AB027464 Frizzled-like receptor homolog(SMO) AF130867 fructosamine 3 kinase AJ404615 Fructose 1,6-bisphosphatase U21931 fumarylacetoacetate hydrolase (fumarylacetoacetase) X51728 G protein-coupled receptor GPR6. U18549 G protein-coupled receptor HM74 (putativeniacin receptor) D10923 G protein-coupled receptor kinase 4(GRK4) L03718 G protein-coupled receptor kinase 5(GRK5) L15388 GABA-B1A receptor AL031983

S42

GABA-B2 receptor AF074483 galactosidase, alpha BC002689 galactosidase, beta 1 M22590 precursor L11144 type 1 (GAL1) L34339 Galanin receptor type 2 (GAL2) AF042782 galectin-3 S59012 Gamma-aminobutyric-acid receptor alpha-4subunit (GABA(A)-A4) U30461 Gamma-aminobutyric-acid receptor alpha-5subunit (GABA(A)-A5) L08485 Gamma-aminobutyric-acid receptor alpha-6subunit (GABA(A)-A6) S81944 Gamma-aminobutyric-acid receptor gamma-2subunit (GABA(A)-C2) X15376 Gamma-glutamyl carboxylase (hGC) AF253530 Gamma-glutamyl hydrolase AF147083 preproprotein X00183 Gastrin-releasing peptide receptor(GRP-preferring ) M73481 GATA binding protein 3 X55122 GATA binding protein 4 L34357 preproprotein J04040 (GL-R) L20316 Glucagon-like peptide 1 receptor (GLP-1R) L23503 Glucagon-like peptide-2 receptor (GLP2R) AF105367 glucocerebrosidase precursor BC003356 receptor (GR) S68378 glucose phosphate BC004982 Glucose transporter type 1(erythrocyte/brain) AF070544 Glucose transporter type 4 (skeletalmuscle - - responsive) M91463 Glucose transporter type 5 (smallintestine) (Fructose transporter) M55531 Glucose-6-phosphatase U01120 glucuronidase, beta M10618 Glutamate [NMDA] receptor subunit 2A U90277 Glutamate [NMDA] receptor subunit 2B U90278 Glutamate [NMDA] receptor subunit 2D U77783 Glutamate [NMDA] receptor subunit epsilon3 L76224 Glutamate [NMDA] receptor subunit zeta 1 L13267 1 (brain, 67kDa)(GAD1) M70434 1 X67491 1 (GLUR-1) M81886 Glutamate receptor 2 (GLUR-2) L20814 Glutamate receptor 5 (GLUR-5 / ionotropickainate 1) L19058 :fructose-6-phosphateamidotransferase (GFAT) M90516 reductase AF228704 Glutathione S-transferase pi (GSTP1) X08094

S43

glycerol-3-phosphate dehydrogenase 1 (soluble) L34041 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) U40367 Glycinamide ribonucleotide transformylase(GARS-AIRS- GART) AF008655 receptor alpha-1 chain X52009 Glycogen synthase kinase-3 alpha (GSK-3alpha) L40027 Glycogen synthase kinase-3 beta (GSK-3beta) L33801 Glycogenin 1 (GYG) AF065481 Glycogenin 2 (GYG2) U94362 glyoxalase I BC001741 -releasing hormone 1 M12578 Gonadotropin-releasing hormone receptor(GNRH-R) Z99995 G-protein coupled receptor 41 (GPR41) AF024688 G-protein-coupled receptor BONZO (STRL33,CXCR6). U73529 Granzyme B (T-cell serine protease 1-3E) M17016 Group IID secretory phospholipase A2(PLA2) AF188625 growth arrest-specific 6 BC038984 growth differentiation factor 8 AF104922 growth factor receptor-bound protein 2 X62852 1 J03071 M28466 growth hormone releasing hormone preproprotein X00094 Growth hormone secretagogue receptor type1 (GHS-R) U60179 Growth hormone-releasing hormone receptor(GHRH receptor) L01406 GTP cyclohydrolase 1 U66095 nucleotide binding protein (G protein), alpha 15 (Gq class) M63904 1, soluble, alpha 2 X63282 guanylate cyclase 1, soluble, beta 2 AF038499 guanylate cyclase 1, soluble, beta 3 X66533 H,K-ATPase beta subunit M75110 Haematopoietic prostaglandin D synthase AB008830 inducible nitric oxide synthase(NOS2D) AF051164 heme oxygenase (decyclizing) 2 BC002396 heparanase AF084467 Hepatic nuclear factor 4 alpha (HNF4A) AF509467 Hepatic triglyceride lipase J03540 Hepatocyte growth factor receptor (METProto-oncogene tyrosine kinase) U19348 Hepatocyte nuclear factor 4-alpha(HNF-4-alpha) AL132772 HERG Potassium Channel AB009071 Hexokinase 4 (HK4 / Glucokinase) M69051 Hexokinase 5 (HK5) AK026414 hexose-6-phosphate dehydrogenase precursor Z98044 High affinity nerve growth factorreceptor (TRK-A) X03541 High-affinity CHT1(SLC5A7) AJ401466 AF026261

S44

Histamine H2 receptor D49783 (JAR4) AF140538 (JAR3) (PFI-13) AB044934 Histamine N-methyltransferase (HNMT) AB041388 decarboxylase X54297 histone deacetylase 5 AK027734 HMG-CoA-synthase U29895 Homo sapiens partial CD95 gene for CD95 antigen, exon 8, cell line RF DI1 (2704). AJ509178 hormone-sensitive lipase U40002 Human urate transporter, URAT1 AC044790 hyaluronan synthase 1 U59269 hyaluronan-mediated motility receptor U29343 hydroxyacyl glutathione hydrolase BC000840 hydroxyacyl-Coenzyme A dehydrogenase, type II BC000372 hydroxysteroid (11-beta) dehydrogenase 2 U26726 Hyperpolarization-activated cationchannel HCN4 AJ132429 hypoxia-inducible factor 1, alpha subunit AF207601 Ig superfamily CTLA-4 U90273 IgE Heavy chain Constant region L00022 IkB kinase alpha subunit (IKK alpha) U22512 IkB kinase beta subunit (IKK BETA) AF029684 Ileal sodium-dependent bile acidtransporter Z54350 Imidazoline (I-1) receptor candidate AB023192 IMP ( monphosphate) dehydrogenasetype 1 J05272 IMP (pyrophosphatephosphoribosyltransferase) M31642 indoleamine-pyrrole 2,3 dioxygenase X17668 Inducible IkappaB kinase IKK-i D63485 Inducible nitric oxide synthase (NOS2A) S75615 M10051 insulin receptor substrate 4 AF007567 Insulin-degrading enzyme(Insulysin/Insulinase) M21188 insulin-like growth factor 1 ( C) M37484 insulin-like growth factor 2 X06161 Insulin-like growth factor bindingprotein 5 protease (HTRA) AF157623 Insulin-like growth factor I receptor X04434 alpha-1 ( and collagenreceptor / VLA-1 / CD49A) Integrin alpha-4 (VLA-4 / CD49D) X16983 Integrin alpha-5 (Fibronectin receptoralpha subunit / VLA-5 / CD49E) X06256 Integrin alpha-7 X74295 Integrin alpha-L (Leukocyte adhesionglycoprotein LFA-1) (CD11A) Y00796 Integrin alpha-M (Leukocyte adhesionreceptor MO1/MAC- 1/CR3) S52227 Integrin alpha-V ( receptoralpha subunit / CD51) AF251841 Integrin beta-1 (Fibronectin receptorbeta subunit) (CD29) (VLA-4 beta) X07979 Integrin beta-2 (Cell surface adhesionglycoproteins LFA- X64072

S45

1/CR3/P150,95 beta subunit) (CD18) Integrin beta-3 (Platelet membraneglycoprotein IIIA / CD61) J02703 Integrin beta-4 (GP150 / CD104) X53587 Integrin-linked kinase (ILK) AJ277481 intercellular adhesion molecule 1 precursor X06990 interferon gamma receptor 1 U19247 interferon, alpha 2 S64994 interferon, beta 1, fibroblast M28622 interferon, omega 1 X58822 interferon-gamma receptor beta chain precursor U05875 interleukin 1 receptor accessory protein AF016261 interleukin 1 AF043143 interleukin 1 receptor, type I precursor X16896 interleukin 1, alpha proprotein CR457414 interleukin 11 precursor AY207429 interleukin 15 precursor receptor precursor U58917 interleukin 18 receptor 1 precursor U43672 interleukin 2 precursor U25676 Interleukin 2 receptor beta chain (p70-75) AL022314 interleukin 20 precursor AF224266 interleukin 21 AF254069 interleukin 3 receptor, alpha precursor D49410 interleukin 5 receptor, alpha precursor interleukin 6 (interferon, beta 2) Y00081 interleukin 6 receptor precursor interleukin 7 precursor M29053 Interleukin-1 receptor-associated kinase(IRAK) L76191 Interleukin-1 receptor-associated kinase4 (IRAK-4) AF155118 Interleukin-4 (IL-4-R) receptor X52425 Intermediate conductancecalcium-activated potassium channel (IK1) AF022150 intestinal fatty acid binding protein 2 M18079 islet amyloid polypeptide precursor X14905 Isoleucyl-tRNA synthetase U04953 ITK/TSK tyrosine kinase S65186 JAR1A (Orphan GPCR - Putativeneurotransmitter receptor) AF021818 JAR5B (Orphan GPCR GPR52) AL022171 JAR6 (Orphan GPCR PFI-7) AY288416 Kappa-type (KOR-1) L36130 Kell blood group glycoprotein S80081 Kinase deficient protein KDP (WNK1) AL049793 kinesin family member 11 X85137 1 M11437 KiSS Receptor AY253982 KIT ligand precursor k-Ras L00048 3-hydroxylase AF056032

S46

lactase- hydrolase preproprotein X07994 lactate dehydrogenase A BC000749 lactate dehydrogenase B BC002362 lactate dehydrogenase C M24515 lactoperoxidase U39573 laminin alpha 3 subunit L34155 receptor U43168 aminopeptidase AF061738 leukemia inhibitory factor receptor precursor X61615 Leukocyte common antigen related protein(LAR) Y00815 Leukocyte elastase ( elastase) M34379 Leukotriene A4 hydrolase J02959 receptor (P2Y purinoceptor7, P2Y7) U33448 2 (BLT2) AB029892 synthase U09353 L-iditol-2 dehydrogenase U67243 LIM domain kinase 1 (LIMK-1) D26309 Lipoprotein Lipase (LPL, Lipase ClearingFactor) M76722 Lipoprotein-associated coagulationinhibitor AF021834 -sensitive myo-inositolmonophosphatase A1 (IMPA1) Y11360 Liver glycogen phosphorylase Y15233 L-kynurenine/alpha-aminoadipateaminotransferase AF097994 Low lipoprotein receptor AF217403 low density lipoprotein receptor-related protein 5 AF064548 low density lipoprotein-related protein 1 Y18524 L-selectin X16070 luteinizing hormone beta subunit precursor X00264 lymphotoxin alpha precursor AB088112 acyltransferasebeta (LPAAT-B) AF011374 Lysosomal carboxypeptidase C (CathepsinA) AL008726 Lysosphingolipid receptor EDG-1 AF022137 Lysosphingolipid receptor EDG-3 X83864 lysyl oxidase preproprotein S78694 Macrophage colony stimulating factor Ireceptor (CSF-1R) U63963 Macrophage migration inhibitory factor(MIF) L19686 MAD, mothers against decapentaplegic homolog 3 U76622 major histocompatibility complex, class II, DR beta 1 precursor X99896 Maltase glucoamylase AF016833 Mannose-6-phosphate isomerase AF227218 mannosidase, alpha, class 1A, member 1 X74837 MAP kinase activated protein kinase 2(MAPKAPK-2) U12779 MAP kinase activated protein kinase 3(MAPKAPK-3) U09578 MAP kinase activated protein kinase 5(MAPKAPK-5) AF032437 Mast/stem cell growth factor receptor(C-KIT) X06182 matrix, extracellular phosphoglycoprotein with ASARM motif (bone) AJ276396 MaxiK channel beta 2 subunit AF099137

S47

MaxiK channel beta subunit U42601 MEK1 L05624 MEK2 BC000471 -concentrating hormone receptor 2(MCH2) AB060151 Melanocortin-1 receptor (Melanocytestimulating hormone receptor MSH-R) X65634 Melanocortin-2 receptor(Adrenocorticotropic hormone receptor ACTH-R) X65633 Melanocortin-3 receptor (MC3-R) L06155 Melanocortin-4 receptor (MC4-R) L08603 Melanocortin-5 receptor (MC5-R) L27080 melanoma cell adhesion molecule AF089868 type 1A (MEL-1A-R) U14108 Melatonin receptor type 1B (MEL-1B-R) U25341 Membrane-associated kinase (MYT1) AF014118 membrane-spanning 4-domains, subfamily A, member 1 X07203 meningioma expressed antigen 5 (hyaluronidase) BC039583 Metabotropic glutamate receptor 1 U31216 Metabotropic glutamate receptor 2 L35318 Metabotropic glutamate receptor 3 AC002081 Metabotropic glutamate receptor 4 U92457 Metabotropic glutamate receptor 5 D28538 Metabotropic glutamate receptor 6 U82083 Metabotropic glutamate receptor 7 U92458 Metabotropic glutamate receptor 8 AJ236922 aminopeptidase 2 U13261 Microsomal glutathione S-transferase 3(MGST3) AF026977 Microsomal triglyceride transfer protein X59657 microtubule-associated protein 1A U14577 microtubule-associated protein tau M25298 receptor (MR) M16801 Misshapen/NIK-related kinase MINK AB035698 Mitochondrial 3-ketoacyl-CoA thiolasebeta-subunit of trifunctional protein (LC 3-KAT) D16481 mitochondrial aldehyde dehydrogenase 2 precursor X05409 Mitochondrial uncoupling protein 3 (UCP3) U82818 Mitochondrial uncoupling protein 4 (UCP4) AF110532 Mitochondrial uncoupling protein 5 (UCP5)(Brain mitochondrial carrier protein-1 BMCP1) AF155811 Mitogen and stress-activated proteinkinase-1 (MSK1) AF080000 Mitogen-activated protein kinase 1 (MAPK1/ ERK2) Z11695 Mitogen-activated protein kinase 10(MAPK10 / JNK3) U34820 Mitogen-activated protein kinase 11(MAPK11 / P38 beta) Y14440 Mitogen-activated protein kinase 12(MAPK12 / ERK6 / P38 gamma) U66243 Mitogen-activated protein kinase 13(MAPK13 / P38 delta) AF100546 Mitogen-activated protein kinase 14(MAPK14 / P38-alpha) L35264 Mitogen-activated protein kinase 8 (MAPK8/ JNK1) U35005 Mitogen-activated protein kinase 9 (MAPK9/ JNK2) U34821

S48

Mitogen-activated protein kinase kinase 3(MAP2K3) U66839 Mitogen-activated protein kinase kinase 4(MAP2K4) L36870 Mitogen-activated protein kinase kinase 6(MAP2K6) U39657 Mitogen-activated protein kinase kinase 7(MAP2K7) AF013589 Mitogen-activated protein kinase kinasekinase 1 (MAP3K1 / MEKK1) AF042838 Mitogen-activated protein kinase kinasekinase 11 (MAP3K11 / Mixed lineage kinase 3) U07747 Mitogen-activated protein kinase kinasekinase 3 (MAP3K3 / MEKK3) U78876 Mitogen-activated protein kinase kinasekinase 7 (MAP3K7) (TAK1) AL121964 Mitogen-activated protein kinase kinasekinase 8 (MAP3K8 / COT) D14497 Mitogen-activated protein kinase kinasekinase kinase 4 (MAP4K4 / HGK) AL137755 MMP-1 (collagenase 1) X54925 MMP-10 (stromelysin 2) X07820 MMP-11 (stromelysin 3) X57766 MMP-12 (metalloelastase) U78045 MMP-13 (collagenase 3) X81640 MMP-14 (MT-MMP 1) X90925 MMP-15 (MT-MMP 2) D86331 MMP-16 (MT-MMP 3) D85511 MMP-2 (gelatinase A) M55593 MMP-26 (endometase) AF230354 MMP-3 (stromelysin 1) X05232 MMP-7 (matrilysin) Z11887 MMP-8 (collagenase 2) J05556 MMP-9 (gelatinase B) J05070 A (MAOA) S72704 Monoamine oxidase B (MAOB) M69177 Monocarboxylate transporter 4 MCT4 U59185 monoglyceride lipase U67963 Receptor (GPR38) AF034632 M-phase inducer phosphatase 1 (cdc25a) M81933 M-phase inducer phosphatase 2 (cdc25b) Z68092 M-phase inducer phosphatase 3 (cdc25c) M34065 MUC1 mucin precursor Mucosal addressin cell adhesionmolecule-1 (MAdCam) AC005775 Multidrug resistance P-glycoprotein 2/3(MDR2/3) M23234 Multidrug resistance protein 2 (MRP2)(MOAT) (ABCC2) AJ132244 Multidrug resistance-associated protein 1(MRP1) (ABCC1) AF022853 Muscarinic acetylcholine receptor M1 M35128 Muscarinic acetylcholine receptor M2 AB041391 Muscarinic acetylcholine receptor M3 AB041395 Muscarinic acetylcholine receptor M4 X15265 Muscarinic acetylcholine receptor M5 AF026263 Muscle glycogen phosphorylase M32598

S49

muscle specific ring finger protein 1 AJ291713 Mu-type opioid receptor (MOR-1) U12569 Myeloperoxidase X15377 light chain kinase AF096773 Na,K-ATPase subunit alpha 1 (Cardiacglycoside target) J03007 Na/K-ATPase beta subunit M25160 Na+/glucose cotransporter 1 (SGLT1) Z74021 NAALADase II protein AJ012370 NADPH Cytochrome P450 reductase AF258341 precursor A K02043 natriuretic peptide precursor B AB037521 NDR protein kinase Z35102 Nerve growth factor receptor M14764 neural cell adhesion molecule 1 U63041 neuregulin 1 -alpha U02330 neurogranin BC002835 Neuromedin K receptor (NKR / NK-3receptor) M89473 receptor NMU1R (aka FM3) AF044601 Neuromedin-B receptor (NMB-R) M73482 Neuronal nitric oxide synthase (NOS1) L02881 Y AC004485 receptor type 1 (NPY1-R) M88461 type 2 (NPY2-R) U50146 Neuropeptide Y receptor type 5 (NPY5-R) U94320 receptor type 1 (NTR1) X70070 type 2 (NTR2) Y10148 neurotensin/ preproprotein U91618 Neutral A(alanine/serine/cysteine/threonine transporter ASCT1) L19444 Neutral endopeptidase (NEP / Neprilysin) Y00811 Neutral sphingomyelinase AF069740 Nicotinic acetylcholine receptor proteinalpha-7 U62436 Nicotinic acetylcholine receptor proteinbeta-2 U62437 N-myristoyltransferase 1 (NMT1) AF020500 L40949 noggin precursor U31202 Non-receptor tyrosine-protein kinase TYK2 X54637 NPC1 (Niemann-Pick disease, type C1, gene)-like 1 AF192523 NPFF2 receptor (NPGPR) AF119815 NT-3 growth factor receptor (TRKC) S76475 Nuclear hormone receptor NOR-1(-derived 1) D85242 Nuclear receptor LXR-alpha U22662 Nuclear receptor NURR1 (Immediate-earlyresponse protein NOT) X75918 Nuclear receptor ROR-alpha-1 U04899 Nuclear receptor ROR-gamma (nuclearreceptor RZR- gamma) U16997

S50

Nucleoside diphosphate kinase A (NDK A)(NM23-H1) X73066 odc1 - ornithine decarboxylase M16650 Oestrogen sulfotransferase (EST-1) Y11195 O-linked GlcNAc transferase AL050366 oncostatin M precursor AC004264 receptor type 1 (OX1R / Hypocretinreceptor type 1) AF041243 type 2 (OX2R / Hypocretinreceptor type 2) AF041245 Orphan GPCR GPR35 AF027957 Orphan GPCR GPR55 AF096786 Orphan GPCR GPR7 U22491 Orphan nuclear receptor HMR (Earlyresponse protein NAK1) D85245 Orphan transporter XT3 AF075260 OX40 receptor S76792 Oxidative-stress responsive 1 AB029024 oxidised low density lipoprotein (lectin-like) receptor 1 AB010710 Oxysterols receptor LXR-beta U07132 (OT-R) X64878 U62768 P Selectin (GMP140/granule membraneprotein-140) M60234 p160ROCK protein kinase (ROCK1) U43195 P2X purinoceptor 1 (P2X1) AF020498 P2X purinoceptor 3 (P2X3) Y07683 P2X purinoceptor 7 (P2X7) Y12851 P2Y purinoceptor 1 (P2Y1) AF018284 P2Y purinoceptor 11 (P2Y11) AF030335 P2Y purinoceptor 6 (P2Y6) U52464 platelet ADP receptor AF313449 p53 cellular tumor antigen AF209148 p53-associated gene (MDM2ubiquitin-protein E3) AJ517838 PAK-alpha kinase (PAK-1) PAK-gamma kinase (PAK-2) U25975 Pancreatic chymotrypsin (caldecrin) Y13697 Pancreatic triacylglycerol lipase L24529 preproprotein J00301 Parathyroid hormone receptor (PTH2receptor) U47129 Parathyroid hormone-related peptidereceptor (PTHR receptor) U17418 PCP-2 Protein tyrosine phosphatase U71075 PDE10A (cAMP-specific phosphodiesterase10A / HSPDE10A) AL117345 PDE11A (cGMP/cAMP-specificphosphodiesterase 11A / HSPDE11A) AJ251509 PDE2A (cGMP-stimulated cGMP/cAMP- specificphosphodiesterase 2A / HSPDE2A) U67733 PDE3A (cGMP-inhibited cAMPphosphodiesterase 3A / HSPDE3A) M91667 PDE3B (cGMP-inhibited cAMPphosphodiesterase 3B / HSPDE3B) X95520

S51

PDE4B (cAMP-specific phosphodiesterase 4B/ HSPDE4B) M97515 PDE4D (cAMP-specific phosphodiesterase 4D/ HSPDE4D) U50157 PDE5A (cGMP-binding, cGMP-specificphosphodiesterase 5A / HSPDE5A) AB015656 PDE6A (cGMP-specific phosphodiesteraserod alpha subunit 6A / HSPDE6A) AF022380 PDE6B (cGMP-specific phosphodiesteraserod beta subunit 6B / HSPDE6B) X62692 PDE6C (cGMP-specific phosphodiesterasecone 6C / HSPDE6C) X94354 PDE7A (cAMP-specific phosphodiesterase7A / HSPDE7A) L12052 PDE7B (cAMP-specific phosphodiesterase 7B/ HSPDE7B) AJ251860 PDE8A (cAMP-specific phosphodiesterase8A / HSPDE8A) AL109778 PDE8B (cAMP-specific phosphodiesterase 8B/ HSPDE8B) AF079529 PDE9A (cGMP-specific phosphodiesterase 9A/ HSPDE9A) AP001747 PDK1 (3-phosphoinositide-dependentprotein kinase-1) AC005591 Pepsin (pepsinogen A) M26032 peptidyl arginine deiminase, type IV AB017919 peptidylprolyl isomerase D D63861 Peripheral receptor (HPBS) L21954 Peroxisome proliferator activatedreceptor alpha (PPAR- alpha) L02932 Peroxisome proliferator activatedreceptor beta (PPAR- beta/delta) AL022721 Peroxisome proliferator activatedreceptor gamma (PPAR- gamma) U79012 hydroxylase U49897 Phenylethanolamine N-methylase (PNMT) J03280 phosphatidylcholine:ceramide cholinephosphotransferase 1 AB154421 Phosphatidylcholine-hydrolyzingphospholipase D2 AF038441 Phosphatidylinositol 3-kinase catalyticsubunit alpha (PI3 kinase alpha) Z29090 Phosphatidylinositol 3-kinase catalyticsubunit gamma (PI3 kinase gamma) X83368 Phosphatidylinositol 3-kinase homolog(ataxia-telangiectasia mutated gene / ATM) Y08455 Phosphatidylinositol-glycan-specificphospholipase D2 AL031230 phosphodiesterase 1A, calmodulin-dependent isoform 2 U40370 phosphodiesterase 1B, calmodulin-dependent U86078 phosphodiesterase 1C, calmodulin-dependent 70kDa U40372 phosphodiesterase 4A, cAMP-specific(phosphodiesterase E2 dunce homolog, Drosophila) (PDE4A) U68532 phosphodiesterase 4C, cAMP-specific(phosphodiesterase E1 dunce homolog, Drosophila) (PDE4C) AC068499 Phosphoenolpyruvate carboxykinase -Cytosolic (PEPCK) L05144 Phosphoenolpyruvate carboxykinase -Mitochondrial (PEPCK) Y11484 Phosphoglycerate kinase 1 V00572 Phosphoinositide-3-kinase, class 2, betapolypeptide (PIK3C2B) Y11312 phospholamban M60411

S52

Phospholipase A2 AC003982 phospholipid transfer protein precursor Phosphorylase B kinase beta regulatorychain X84908 Phosphoserine aminotransferase (PSA) AF113132 Pituitary adenylate cyclase activatingpolypeptide type i receptor (PACAP-R-1) D17516 Plasma kallikrein M13143 Plasminogen M74220 Plasminogen activator inhibitor-1 (PAI-1) X04729 plasminogen activator, urokinase receptor precursor Platelet activating factor receptor(PAF-R) D10202 platelet factor 4 variant 1 M26167 platelet/endothelial cell adhesion molecule (CD31 antigen) AF281290 platelet-derived growth factor beta , preproprotein X02744 pleiotrophin S60110 PLK1 kinase U78073 Poly(ADP-) polymerase (PARP) X56140 polyamine oxidase AK025938 polymerase (DNA directed), beta D29013 potassium channel, subfamily K, member 3 (KCNK3) (TASK-1) AF110524 potassium channel, subfamily K, member 4 (KCNK4) (TRAAK) AF247042 potassium channel, subfamily K, member 5 (KCNK5) (TASK-2) AF084830 potassium channel, subfamily K, member 9 (KCNK9) (TASK-3) AF279809 PP1-alpha Serine/threonine proteinphosphatase M63960 PP1-beta Serine/threonine proteinphosphatase AF092905 PP1-gamma Serine/threonine proteinphosphatase AB030255 Prenylcysteine carboxyl methyltransferase(PCCMT) AF064084 Presenilin 1 (PS-1) AF109907 Presenilin 2 (PS-2) U50871 Presynaptic protein SAP97 U13896 prion protein preproprotein AF085477 proenkephalin V00509 Progastricsin (Pepsinogen C) M18667 (PR) AF016381 proliferating cell nuclear antigen J04718 Prolyl endopeptidase AB020018 pro-melanin-concentrating hormone M57703 preproprotein M38297 receptor ( IPreceptor) D38128 receptor (prostanoid DPreceptor) U31332 Prostaglandin E synthase AF010316 receptor EP1 subtype(Prostanoid EP1 receptor) L22647 Prostaglandin E2 receptor EP2 subtype(Prostanoid EP2 receptor) AF134202

S53

Prostaglandin E2 receptor EP3 subtype(Prostanoid EP3 receptor) D86097 Prostaglandin E2 receptor EP4 subtype(Prostanoid EP4 receptor) X97873 Prostaglandin F2-alpha receptor(Prostanoid FP receptor) AB041713 prostaglandin H2 D-isomerase M98538 Prostate specific antigen (PSA) M26663 Prostate-specific membrane antigen (PSM) AF254357 protease, serine, 23 AF193611 protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1 BC002899 alpha X07767 Protein kinase C alpha type (PKC-alpha) Protein kinase C beta-I type(PKC-beta-1) X07109 Protein kinase C delta type (NPKC-delta) Protein kinase C epsilon type(NPKC-epsilon) X65293 Protein kinase C eta type (NPKC-eta)(PKC-L) Protein kinase C gamma type (PKC-gamma) Protein kinase C theta type (NPKC-theta) Protein kinase C zeta type (NPKC-zeta) Protein kinase C-like 1 D26181 Protein tyrosine phosphatase 1B M31724 Protein tyrosine phosphatase alpha X54890 Protein tyrosine phosphatase delta S78086 Protein tyrosine phosphatase epsilon X54134 Protein tyrosine phosphatase eta (DEP-1)(CD148) U10886 Protein tyrosine phosphatase zeta U88967 Proteinase activated receptor 2 (PAR-2) Z49993 prothymosin, alpha (gene sequence 28) AF348514 Proton-gated cation channel subunit(ASIC3) AF057711 Proto-oncogene FES tyrosine kinase X06292 Proto-oncogene FYN tyrosine kinase S74774 Proto-oncogene kinase PIM-1 M24779 Proto-oncogene LCK tyrosine kinase U07236 Proto-oncogene tyrosine-protein kinasereceptor RET AJ243297 Proto-oncogene tyrosine-protein kinaseYES M15990 phosphorylase (PNP) M13953 Puromycin-sensitive aminopeptidase (PSA) Y07701 Putative chemokine receptor FKSG80 (GPR81) BC066883 pyruvate carboxylase precursor U30891 Pyruvate dehydrogenase kinase 1 (PDK1) L42450 Pyruvate dehydrogenase kinase 2 (PDK2) L42451 Pyruvate dehydrogenase kinase 3 (PDK3) L42452 Pyruvate dehydrogenase kinase 4 (PDK4) AC002451 RAC-alpha serine/threonine kinase(Protein kinase B) X61037 RAC-beta serine/threonine kinase (AKT2kinase) M95936 RAR gamma AJ250835 ras homolog gene family, member A M83094

S54

Receptor protein-tyrosine kinase TKT(TYRO 10) X74764 reelin U79716 regulator of G-protein signaling 4 BC000737 regulator of G-protein signalling 2, 24kDa L13463 1 preproprotein X00949 (Angiotensinogenase) X00063 Retinoic acid receptor alpha (RAR-alpha) M73779 Retinoic acid receptor beta-2(RAR-beta-2) M57445 Retinoic acid receptor RXR-alpha X52773 Retinoic acid receptor RXR-beta X63522 Retinoic acid receptor RXR-gamma AL160058 Ribonuclease A (RNase A) S79281 Ribosomal protein S6 kinase M60724 Ribosomal protein S6 kinase II alpha 1 L07597 Ribosomal protein S6 kinase II alpha 3 U08316 RIP2 kinase (RICK) AF078530 runt-related transcription factor 2 AF001450 Ryanodine receptor 1 M91455 Ryanodine receptor 3 AJ001515 S-adenosylhomocysteine hydrolase (AHCY) M61832 S-adenosylmethionine decarboxylase M21154 SAK protein kinase Y13115 sapiens solute carrier family 7 (cationicamino acid transporter, y+ system), member 5 (SLC7A5) AB018542 scavenger receptor class B, member 1 Z22555 sclerostin precursor AF326736 preproprotein AF244355 (SCT-R) U28281 selectin P ligand U02297 selenoprotein S AF328864 serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1 X00237 serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 U57450 Serine protease OMI AF141307 Serine/threonine kinase Akt-3 (Proteinkinase B gamma) AJ245709 Serine/threonine protein kinase MARK AF154845 Serine/threonine protein kinase P78 U64205 Serine/threonine protein kinase PAK4 AJ011855 Serine/threonine protein kinase PIM-2 D84454 Serine/threonine protein kinase PRK U56998 Serine/threonine protein phosphatase 2Balpha (Calcineurin A alpha) L14778 serpin peptidase inhibitor, clade A, member 3 precursor M18906 Serum glucocorticoid-regulated kinase 1(SGK) (SGK1) AJ000512 Serum-inducible kinase (SNK) U85755 -binding globulin X16349 SH2-containing polyphosphate5-phosphatase 2 (SHIP-2) L24444

S55

sialophorin J04536 Sigma opioid receptor AF226604 signal transducer and activator of transcription 3 AF029311 signal transducer and activator of transcription 6 U66574 signaling lymphocytic activation molecule family member 1 AL121985 similar to Apolipoprotein A-I precursor (Apo-AI) M11791 single-minded homolog 2 long isoform U80457 Site 1 Protease (S1P) AL133583 Sodium and chloride-dependent GABAtransporter 1 (GAT1) X54673 Sodium and chloride-dependent GABAtransporter 2 (GAT2) U76343 Sodium and chloride-dependent GABAtransporter 3 (GAT3) S75989 Sodium and chloride-dependent glycinetransporter 1 (GLYT1) S70612 Sodium and chloride-dependentbetaine/GABA transporter (BGT1) L42300 Sodium channel protein I alpha subunit (NaV1.1) X65362 Sodium/glucose co-transporter 2 (SGLT2) M95549 Sodium/hydrogen exchanger isoform 1(NHE1) AF141357 Sodium/hydrogen exchanger isoform 2(NHE2) S83549 Sodium-dependent (DAT) S46955 Sodium-dependent glutamate/aspartatetransporter 1 (EAAT1) D26443 Sodium-dependent noradrenalinetransporter (NAT) X91117 Sodium-dependent transporter S80071 Sodium-dependent transporter(5HTT) X70697 Soluble guanylate cyclase alpha 1 (sGCalpha 1) U58855 solute carrier family 2 (facilitatedglucose transporter), member 10; transporter GLUT10 AL031055 solute carrier family 22 (organic cationtransporter), member 2 (SLC22A2) X98333 solute carrier family 22 (organic cationtransporter), member 4 (SLC22A4) AB007448 solute carrier family 22 (organic cationtransporter), member 5 (SLC22A5) AF057164 solute carrier organic anion transporterfamily, member 1B1 (SLCO1B1) AJ132573 solute carrier organic anion transporterfamily, member 1B3 (SLCO1B3) AJ400763 preproprotein J00306 type 1 (SS1R) M81829 Somatostatin receptor type 2 (SS2R) AF184174 Somatostatin receptor type 3 (SS3R) Z82188 Somatostatin receptor type 4 (SS4R) D16826 Somatostatin receptor type 5 (SS5R) AL031713 synthase (SRM) (Putrescineaminopropyltransferase) M34338 sphingomyelin phosphodiesterase 2, neutral membrane (neutral sphingomyelinase) AJ222801 Sphingosine kinase SPHK1 AF266756 Squalene epoxidase (ERG1) AF098865

S56

Squalene synthetase (ERG9) S76822 SRC Kinase X02647 SREBP cleavage-activating protein D83782 stearoyl-CoA desaturase AB032261 Steroid 17-alpha-hydroxylase M63871 Steroid 5-alpha-reductase AF113128 Steroid hormone receptor ERR1(Estrogen-related receptor alpha) X51416 Steroid hormone receptor ERR2(Estrogen-related receptor beta) X51417 Steroid sulfatase (STS) J04964 Steroidogenic factor 1 (STF-1) D88155 sterol carrier protein 2 precursor sterol regulatory element binding transcription factor 1 U00968 sterol regulatory element-binding transcription factor 2 AL021453 Substance-K receptor (SKR / NK-2 receptor) M57414 Substance-P receptor (SPR / NK-1 receptor) M81797 Subtilisin-like protease PACE4 D28514 Succinate receptor AF348078 sucrase-isomaltase (alpha-glucosidase) M22616 Sulfotransferase 1C2 (SULT1C2) AF186263 SYK tyrosine kinase L28824 Synaptic vesicle protein 2A (SV2A)(KIAA0736) AB018279 syndecan 1 precursor BC008765 tachykinin 1 precursor T-cell (cyclophilin A) X52851 T-cell protein tyrosine phosphatase M25393 Telomerase reverse transcriptase (hTRT) AB016767 Testisin (TEST1) AB031331 TGF-beta receptor type I (TGFR-1 /Activin receptor-like kinase 5 / ALK-5) AF035670 TGF-beta receptor type II (TGFR-2) D28131 Thiazide-sensitive Na-Cl cotransporter U44128 S76625 thrombomodulin precursor AL049651 thrombopoietin precursor M90102 A2 receptor (TXA2-R)(prostanoid TP receptor) D38081 Thy-1 cell surface antigen AF261093 Thymidine phosphorylase (platelet-derivedendothelial cell growth factor) U62317 Thymidylate synthase D00596 Thyroid hormone receptor alpha-1(C-ERBA-alpha-1 / EAR7) M24748 M55702 Thyroid receptor beta M26747 (TSH-R) AC007262 thyrotropin-releasing hormone M63582 Thyrotropin-releasing hormone degradingectoenzyme AF126372

S57

(TRHDE) Thyrotropin-releasing hormone receptor(TRH-R) X75071 tissue inhibitor of metalloproteinase 4 precursor U76456 Tissue plasminogen activator (TPA) L00153 Tissue Transglutaminase (Transglutaminase2/TGM2) M98478 TNF receptor-associated factor 2 U12597 TNF-R (tumor necrosis factor receptortype 1) M60275 toll-like receptor 2 U88878 toll-like receptor 4 U88880 toll-like receptor 7 AF240467 toll-like receptor 9 precursor Tolloid-like protein (TLL) AF282732 Topoisomerase I AL035652 Topoisomerase II AF285158 transcription factor SOX9 Z46629 transferrin AF118063 transforming growth factor, alpha AF123243 transforming growth factor, beta 1 X02812 transforming growth factor, beta 2 M87843 transforming growth factor, beta 3 AY208161 transient receptor potential cationchannel, subfamily V, member 1 (TRPV1) AJ277028 transient receptor potential cationchannel, subfamily V, member 2 (TRPV2) AF129112 transient receptor potential cationchannel, subfamily V, member 4 AX026851 tripartite motif protein TRIM5 AF220025 Tripeptidyl peptidase II (TPP II) M73047 troponin C, slow X07897 troponin T type 2, cardiac L40162 TRP-like channel MTR1 (MTR5) AJ270996 2,3-dioxygenase U32989 1 AF057280 tumor necrosis factor (ligand) superfamily, member 10 U57059 tumor necrosis factor ligand superfamily, member 11 AF019047 tumor necrosis factor receptor superfamily, member 8 precursor tumor-associated calcium signal transducer 1 precursor M32306 Tumour necrosis factor (TNF-alpha) AB088112 TXK tyrosine kinase L27071 Type I 5-prime iodothyronine deiodinase AL031427 Type-1 angiotensin II receptor (AT1) Z11162 Type-2 angiotensin II receptor (AT2) U20860 Tyrosinase J03581 Tyrosine aminotransferase (TAT) X55675 M23597 Tyrosine-protein kinase ACK L13738 Tyrosine-protein kinase HCK (Haemopoieticcell kinase) AL049539 Tyrosine-protein kinase JAK1 (JANUSKINASE 1) M64174

S58

Tyrosine-protein kinase JAK2 (JANUSKINASE 2) AF058925 Tyrosine-protein kinase JAK3 (JANUSKINASE 3) U09607 Tyrosine-protein kinase LYN M79321 Tyrosine-protein kinase receptor TYRO3(RSE) (SKY) X72886 Tyrosine-protein kinase RYK X96588 UDP-Gal:betaGlcNAc beta1,4-galactosyltransferase 2 (B4GALT2) AB024434 UDP-glucose ceramide glucosyltransferase(UGCG) D50840 UDP-glucuronosyltransferase 2 B28(UGT2B28) AF177272 monophosphate synthase BC000364 Uridine nucleotide receptor (UNR) U40223 uridine phosphorylase 1 BC001405 Urokinase-type plasminogen activator(UPA) K02286 Urotensin II receptor (GPR14) AF140631 Vascular cell adhesion protein 1 (VCAM1) M30257 vascular endothelial growth factor precursor vascular endothelial growth factor C preproprotein X94216 Vascular endothelial growth factorreceptor 1 (VEGFR-1 / FLT1) X51602 Vascular endothelial growth factorreceptor 2 (VEGFR-2 / FLK1) L04947 Vascular endothelial growth factorreceptor 3 (VEGFR-3 / FLT4) X68203 vasoactive intestinal peptide preproprotein Vasoactive intestinal polypeptide receptor1 (VIP-R-1) U11087 Vasoactive intestinal polypeptide receptor2 (VIP-R-2) X95097 Vasopressin V1A receptor U19906 Vasopressin V1b receptor L37112 Vasopressin V2 receptor AF101728 vav 1 oncogene X83931 Vesicular acetylcholine transporter U10554 Vesicular VMAT2 L23205 Vitamin D3 receptor (VDR /1,25-dihydroxyvitamin D3 receptor) M65208 v-jun avian sarcoma virus 17 oncogene homolog J04111 v-myb myeloblastosis viral oncogene homolog (avian)-like 1 X13294 Voltage-gated potassium channel KV1.1 L02750 Voltage-gated potassium channel KV1.5 M60451 Voltage-gated sodium channel (SCN10A, PN3, Nav1.8) AF117907 Voltage-gated sodium channel subtype II (NaV1.2) M94055 von Willebrand factor precursor M25865 WEE1-like protein kinase U10564 White homolog (ABCG1) AP001746 dehydrogenase/oxidase U06117 X-prolyl aminopeptidase (aminopeptidaseP) 2, membrane- bound AL023653 ZAP-70 tyrosine kinase AB083211

S59

Supplementary Figure 3: 1082 COSTART Terms

ABDOMINAL PAIN ABNORMAL DREAMS ABNORMAL EJACULATION ABNORMAL ELECTROENCEPHALOGRAM ABNORMAL GAIT ABNORMAL LABOR ABNORMAL ABNORMAL STOOLS ABNORMAL VISION ABSCESS ACCIDENTAL FALL ACCIDENTAL INJURY ACCIDENTAL OVERDOSE ACHLORHYDRIA ACID PHOSPHATASE INCREASED ACIDOSIS ACNE ACRODYNIA ACUTE BRAIN SYNDROME ACUTE KIDNEY FAILURE ACUTE LEUKEMIA ACUTE LYMPHOBLASTIC LEUKEMIA ACUTE MONOBLASTIC LEUKEMIA ACUTE MYELOBLASTIC LEUKEMIA ADAMS STOKES SYNDROME ADDICTION ADDISONIAN CRISIS ADENOMA ADRENAL CORTEX ATROPHY ADRENAL CORTEX HYPERPLASIA ADRENAL CORTEX NECROSIS ADRENAL DISORDER ADRENAL HEMORRHAGE AGITATION AGRANULOCYTOSIS AIDS AKATHISIA AKINESIA ALBUMINURIA ALCOHOL INTOLERANCE ALDOSTERONE INCREASED ALKALINE PHOSPHATASE INCREASED ALKALOSIS ALLERGIC MYOCARDITIS

S60

ALLERGIC REACTION ALOPECIA AMBLYOPIA AMENORRHEA AMNESIA AMYLASE INCREASED AMYLOIDOSIS ANAPHYLACTOID REACTION ANEMIA ANGINA PECTORIS ANGIOEDEMA ANISOCORIA ANOREXIA ANOREXIA NERVOSA ANORGASMIA SYNDROME ANTISOCIAL REACTION ANURIA ANXIETY AORTIC STENOSIS APATHY APHASIA APHTHOUS STOMATITIS APLASTIC ANEMIA APNEA APPLICATION SITE REACTION ARACHNOIDITIS ARRHYTHMIA ARTERIAL ANOMALY ARTERIAL ARTERIOSCLEROSIS ARTERIOSPASM ARTERITIS ARTHRALGIA ARTHRITIS ARTHROSIS ASCITES ASPHYXIA ASPIRATION PNEUMONIA ASTHENIA ASTHMA ATAXIA ATELECTASIS ATRIAL ARRHYTHMIA ATRIAL FIBRILLATION ATRIAL FLUTTER

S61

ATRIAL SEPTAL DEFECT ATROPHIC RHINITIS AV BLOCK AV BLOCK COMPLETE AV BLOCK SECOND DEGREE AVITAMINOSIS B12 DEFICIENCY ANEMIA BACK PAIN BACTERIAL RESISTANCE BALANITIS INTOXICATION BASOPHILIA BEING QUERIED BEZOAR BIGEMINY BILIARY ATRESIA BILIARY PAIN BILIRUBINEMIA BILIRUBINURIA BIPOLAR AFFECTIVE DISORDER - DEPRESSIVE BIPOLAR AFFECTIVE DISORDER - MANIC BLADDER CALCULUS BLADDER CARCINOMA BLADDER NEOPLASM BLADDER PAIN BLEEDING TIME DECREASED BLEEDING TIME INCREASED BLEPHARITIS BLINDNESS BLOOD DYSCRASIA BLOODY DIARRHEA BODY ODOR BONE DISORDER BONE NECROSIS BONE NEOPLASM BONE PAIN BONE SARCOMA BRADYCARDIA BRAIN ABSCESS BRAIN EDEMA BRAIN STEM DISORDER BREAST ABSCESS BREAST ATROPHY BREAST CARCINOMA BREAST ENGORGEMENT BREAST ENLARGEMENT

S62

BREAST NEOPLASM BREAST PAIN BROMISM BRONCHIECTASIS BRONCHIOLITIS BRONCHITIS BRONCHOSTENOSIS BRUISE BUN INCREASED BUNDLE BRANCH BLOCK BURSITIS CACHEXIA CALCIUM DISORDER CARCINOMA CARCINOMA OF LARYNX CARCINOMA OF LUNG CARCINOMA OF MOUTH CARDIOMEGALY CARDIOMYOPATHY CARDIOSPASM CARDIOVASCULAR DISORDER CAROTID OCCLUSION CAROTID THROMBOSIS CARPAL TUNNEL SYNDROME CATATONIC REACTION CELLULITIS CEREBELLAR ATAXIA CEREBELLAR SYNDROME CEREBRAL ARTERIAL THROMBOSIS CEREBRAL EMBOLISM CEREBRAL HEMORRHAGE CEREBRAL INFARCT CEREBRAL ISCHEMIA CEREBRAL THROMBOSIS CEREBRAL VENOUS THROMBOSIS CEREBROVASCULAR ACCIDENT CEREBROVASCULAR DISORDER CERVICAL POLYP CERVICITIS CERVIX CARCINOMA CHEILITIS CHEST PAIN CHILLS CHILLS AND CHLOASMA CHOLANGITIS

S63

CHOLECYSTITIS CHOLELITHIASIS CHOLESTATIC JAUNDICE SYNDROME DECREASED CHOLINESTERASE INCREASED CHONDRODYSTROPHY CHOREOATHETOSIS CHORIORETINITIS CHOROIDITIS CHROMATOPSIA ABNORMALITY CHRONIC BRAIN SYNDROME CHRONIC LEUKEMIA CHRONIC LYMPHOCYTIC LEUKEMIA CHRONIC MONOCYTIC LEUKEMIA CHRONIC MYELOCYTIC LEUKEMIA CINCHONISM CIRCULATION DISORDER CIRCUMORAL PARESTHESIA CIRRHOSIS OF LIVER CLEFT LIP CLEFT PALATE CLUBFOOT CNS DEPRESSION CNS NEOPLASIA CNS STIMULATION COAGULATION DISORDER COAGULATION TIME DECREASED COAGULATION TIME INCREASED COGWHEEL RIGIDITY COLITIS DISORDER COLOR BLINDNESS COMA CONFUSION CONGENITAL ANOMALY CONGESTIVE HEART FAILURE CONJUNCTIVAL EDEMA CONJUNCTIVAL ULCER CONJUNCTIVITIS CONSTIPATION CONTACT DERMATITIS CONVULSION COR PULMONALE CORNEAL LESION

S64

CORNEAL OPACITY CORNEAL PERFORATION CORNEAL ULCER CORONARY EMBOLISM CORONARY OCCLUSION CORONARY THROMBOSIS COUGH DECREASED COUGH INCREASED CREATINE PHOSPHOKINASE INCREASED CREATININE CLEARANCE DECREASED CREATININE INCREASED CRETINISM CRYPTOCOCCOSIS CRYSTALLURIA CUSHING'S SYNDROME CUTANEOUS MONILIASIS CYANOSIS CYST CYSTITIS DEAFNESS DEATH DEATH BY SUICIDE DEATH FETAL DECREASED EFFECT DECREASED URINE FLOW DEEP PHLEBITIS DEEP THROMBOPHLEBITIS DEHYDRATION DELIRIUM DELUSIONS DEMENTIA DEPERSONALIZATION DEPRESSION DERMATITIS DERMATOMYOSITIS DIABETES INSIPIDUS DIABETES MELLITUS DIABETIC ACIDOSIS DIABETIC COMA DIARRHEA DIC DIGITALIS INTOXICATION DIPLOPIA DISCOID LUPUS ERYTHEMATOSIS DIVERTICULITIS DIVERTICULOSIS

S65

DIZZINESS DEPENDENCE DRUG INTERACTION DRUG LEVEL DECREASED DRUG LEVEL INCREASED DRUG TOXICITY DRY EYES DRY MOUTH DRY SKIN DUODENAL ULCER DUODENAL ULCER HEMORRHAGE DUODENAL ULCER PERFORATION DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION DUODENITIS DWARFISM DYSARTHRIA DYSAUTONOMIA DYSKINESIA DYSMENORRHEA DYSPAREUNIA DYSPEPSIA DYSPHAGIA DYSPNEA DYSTONIA DYSURIA EAR DISORDER EAR PAIN ECCHYMOSIS ECTOPIA CORDIS ECTROMELIA ECZEMA EDEMA EJACULATION RETROGRADE ELECTROCARDIOGRAM ABNORMAL ELECTROLYTE ABNORMALITY ELECTROLYTE DEPLETION EMBOLUS EMOTIONAL LABILITY EMPHYSEMA ENANTHEMA ENCEPHALITIS ENCEPHALOCELE ENCEPHALOPATHY ENDOCARDITIS ENDOCRINE DISORDER ENDOMETRIAL CARCINOMA

S66

ENDOMETRIAL DISORDER ENDOMETRIAL HYPERPLASIA ENDOMETRIAL NEOPLASIA ENDOMETRIAL POLYP ENDOMETRIAL THICKENING ENLARGED CLITORIS ENTERITIS ENTEROCOLITIS ENZYMATIC ABNORMALITY EOSINOPHILIA EOSINOPHILIC PNEUMONIA EPENDYMITIS EPIDERMAL NECROLYSIS EPIDIDYMITIS EPISTAXIS ERUCTATION ERYTHEMA MULTIFORME ERYTHEMA NODOSUM ERYTHROID MATURATION ARREST ESOPHAGEAL HEMORRHAGE ESOPHAGEAL STENOSIS ESOPHAGEAL ULCER ESOPHAGITIS EUPHORIA EXFOLIATIVE DERMATITIS EXOPHTHALMOS EXPOSURE TO DISEASE EXTRAPYRAMIDAL SYNDROME EXTRASYSTOLES EYE DISORDER EYE HEMORRHAGE EYE PAIN FACE EDEMA FACIAL PARALYSIS FALSE POSITIVE PREGNANCY TEST FANCONI-LIKE SYNDROME FEBRILE NEUTROPENIA FECAL IMPACTION FECAL INCONTINENCE FEELING OF RELAXATION FEMINIZATION FETAL DISORDER FEVER FIBRIN DECREASED FIBRIN INCREASED FIBRINOGEN DECREASED

S67

FIBRINOGEN INCREASED FIBRINOLYSIS DECREASED FIBRINOLYSIS INCREASED FIBROCYSTIC BREAST FIXED ERUPTION FLACCID PARALYSIS FLANK PAIN FLATULENCE FLU SYNDROME FLUOROSIS FOLATE DEFICIENCY ANEMIA FOLLICULITIS FOOT DROP FUNGAL DERMATITIS FURUNCULOSIS GAMMA GLOBULINS INCREASED GAMMA GLUTAMYL TRANSPEPTIDASE INCREASED GANGRENE GASTRITIS GASTROENTERITIS GASTROINTESTINAL ANOMALY GASTROINTESTINAL CARCINOMA GASTROINTESTINAL DISORDER GASTROINTESTINAL HEMORRHAGE GENERALIZED EDEMA GENERALIZED SPASM GENITAL EDEMA GENITAL MONILIASIS GI NEOPLASM GI PERFORATION GIGANTISM GINGIVITIS GLAUCOMA GLOBULIN DECREASED GLOBULIN INCREASED GLOMERULITIS GLOSSITIS INCREASED GLUCOSE TOLERANCE DECREASED GLYCOSURIA GOITER DECREASED GONADOTROPINS INCREASED GOUT GRAFT VS. HOST REACTION GRAND MAL CONVULSION

S68

GRANULOCYTOSIS GRANULOMA GROWTH ACCELERATED GROWTH RETARDED GUILLAIN BARRE SYNDROME GUM HYPERPLASIA GYNECOMASTIA HAIR DISCOLORATION HAIR DISORDER HALITOSIS HALLUCINATIONS HANGOVER EFFECT HEADACHE HEALING ABNORMAL HEART ARREST HEART BLOCK HEART FAILURE HEART MALFORMATION HEAT STROKE HEINZ BODIES HEMATEMESIS HEMATURIA HEMIPLEGIA HEMOCHROMATOSIS HEMOLYSIS HEMOLYTIC ANEMIA HEMOPERICARDIUM HEMOPERITONEUM HEMOPTYSIS HEMORRHAGE HEMORRHAGIC COLITIS HEMORRHAGIC CYSTITIS HEMORRHAGIC ENTEROCOLITIS HEMORRHAGIC GASTRITIS HEMORRHAGIC PANCREATITIS HEMORRHAGIC PROCTITIS HEMOSIDEROSIS HEMOTHORAX HEPATIC COMA HEPATIC INCREASED HEPATIC FAILURE HEPATIC NEOPLASIA HEPATITIS HEPATOMA HEPATOMEGALY HEPATORENAL SYNDROME

S69

HEPATOSPLENOMEGALY HERMAPHRODITISM HERNIA HERPES SIMPLEX HERPES ZOSTER HICCUP HIGH DENSITY LIPOPROTEIN DECREASED HIGH DENSITY LIPOPROTEIN INCREASED HIRSUTISM HIV INFECTION/DISEASE HIV TEST POSITIVE HOSTILITY HOT FLUSHES HYDROCEPHALUS HYDRONEPHROSIS HYDROURETER HYPALGESIA HYPERACUSIS HYPERALGESIA HYPERAMMONEMIA HYPERCALCEMIA HYPERCHLOREMIA HYPERCHLOREMIC ACIDOSIS HYPERCHLORHYDRIA HYPERCHOLESTEREMIA HYPERESTHESIA HYPERGLYCEMIA HYPERKALEMIA HYPERKINESIA HYPERLIPEMIA HYPERMAGNESEMIA HYPERNATREMIA HYPERPHOSPHATEMIA HYPERTENSION HYPERTENSIVE ENCEPHALOPATHY HYPERTHYROIDISM HYPERTROPHY HYPERURICEMIA HYPERVENTILATION HYPERVOLEMIA HYPESTHESIA HYPOACUSIS HYPOCALCEMIA HYPOCALCEMIC TETANY HYPOCHLOREMIA HYPOCHLOREMIC ALKALOSIS

S70

HYPOCHOLESTEREMIA HYPOCHROMIC ANEMIA HYPOGLYCEMIA HYPOGLYCEMIC REACTION HYPOGONADISM FEMALE HYPOGONADISM MALE HYPOKALEMIC ALKALOSIS HYPOKINESIA HYPOLIPEMIA HYPOMAGNESEMIA HYPOMENORRHEA HYPONATREMIA HYPOPHOSPHATEMIA HYPOPLASTIC ANEMIA HYPOPROTEINEMIA HYPOTENSION HYPOTHERMIA HYPOVENTILATION HYPOVOLEMIA HYPOXIA HYSTERIA ICHTHYOSIS ILEITIS ILEUS IMMUNE SYSTEM DISORDER IMMUNOGLOBULINS DECREASED IMMUNOGLOBULINS INCREASED IMPERFORATE ANUS IMPOTENCE INCOORDINATION INCREASED ANTICOAGULANT EFFECT INCREASED APPETITE INCREASED CAPILLARY FRAGILITY INCREASED DRUG EFFECT INCREASED SALIVATION INDIRECT COOMBS TEST POSITIVE INFECTION INFECTION BACTERIAL INFECTION FUNGAL INFECTION MASKED INFECTION PARASITIC INFECTION SUPERIMPOSED INJECTION SITE HEMORRHAGE INSOMNIA

S71

INTENTIONAL OVERDOSE INTERSTITIAL PNEUMONIA INTESTINAL GANGRENE INTESTINAL NECROSIS INTESTINAL OBSTRUCTION INTESTINAL PERFORATION INTESTINAL STENOSIS INTESTINAL ULCER INTRACRANIAL ANEURYSM INTRACRANIAL HEMORRHAGE INTRACRANIAL HYPERTENSION IODISM IRITIS IRON DEFICIENCY ANEMIA IRRITABILITY ISCHEMIC COLITIS JAUNDICE JOINT DISORDER KERATITIS KERATOCONJUNCTIVITIS KETOSIS KIDNEY ABSCESS KIDNEY CALCULUS KIDNEY CORTEX NECROSIS KIDNEY FAILURE KIDNEY FIBROSIS KIDNEY PAIN KIDNEY TUBULAR NECROSIS KIDNEY VASCULITIS LABIAL EDEMA LABILE BLOOD PRESSURE LACK OF DRUG EFFECT LACTATION DECREASED LACTIC ACIDOSIS LACTIC DEHYDROGENASE INCREASED LARYNGISMUS LARYNGITIS LARYNX EDEMA LE SYNDROME LEFT HEART FAILURE LEG CRAMPS LESION LEUKEMIA LEUKEMOID REACTION LEUKOCYTOSIS LEUKODERMA

S72

LEUKOPENIA LEUKORRHEA LIBIDO DECREASED LIBIDO INCREASED LICHENOID DERMATITIS LIPASE INCREASED LIPID PNEUMONIA LIPODYSTROPHY LIPOMA LIVER DAMAGE LIVER FUNCTION TESTS ABNORMAL LIVER NECROSIS LIVER TENDERNESS LUNG DISORDER LUNG EDEMA LUNG FIBROSIS LUNG FUNCTION DECREASED LUNG HEMORRHAGE LYMPHADENOPATHY LYMPHANGITIS LYMPHEDEMA LYMPHOCYTOSIS LYMPHOMA MALIGNANT MACROCYTIC ANEMIA MACULOPAPULAR RASH MALABSORPTION SYNDROME MALAISE MALIGNANT HYPERTHERMIA MANIC REACTION MARROW DEPRESSION MARROW HYPERPLASIA MASKED FACIES MEDIASTINAL FIBROSIS MEDICATION ERROR MEGACOLON MEGAKARYOCYTES INCREASED MEGALOBLASTIC ANEMIA MELANOSIS MELENA MENINGISM MENINGITIS MENINGOMYELOCELE MENOPAUSE MENORRHAGIA MENSTRUAL DISORDER MENTAL DETERIORATION

S73

MENTAL RETARDATION MESENTERIC ARTERIAL OCCLUSION MESENTERIC FIBROSIS MESENTERIC OCCLUSION MESENTERIC VENOUS OCCLUSION METHEMOGLOBINEMIA METHEMOGLOBINURIA METRORRHAGIA MICROCYTIC ANEMIA MIGRAINE MILIARIA MIOSIS MISCARRIAGE MONILIASIS MONOCYTOSIS MONOPLEGIA MOTOR VEHICLE ACCIDENT MOUTH ULCERATION MOVEMENT DISORDER MULTIFOCAL EXTRASYSTOLES MULTI-ORGAN FAILURE MULTIPLE CONGENITAL ANOMALIES MULTIPLE PREGNANCY MULTIPLE SCLEROSIS MUSCLE ATROPHY MUSCULAR HYPERTONIA MUSCULAR HYPOTONIA MYALGIA MYASTHENIA MYDRIASIS MYELITIS MYELOFIBROSIS MYELOID MATURATION ARREST MYELOID METAPLASIA MYELOMA MYELOPROLIFERATIVE DISORDER MYOCARDIAL FIBROSIS MYOCARDIAL INFARCT MYOCARDIAL ISCHEMIA MYOCARDITIS MYOCLONUS MYOPATHY MYOSITIS NAIL DISORDER NASAL POLYP NAUSEA

S74

NAUSEA AND VOMITING NAUSEA VOMITING AND DIARRHEA NECK PAIN NECK RIGIDITY NECROSIS NECROTIZING PANCREATITIS NEONATAL JAUNDICE NEOPLASM NEPHRITIS NEPHROCALCINOSIS NEPHROSCLEROSIS NEPHROSIS NERVOUSNESS NEURALGIA NEURITIS NEUROLEPTIC MALIGNANT SYNDROME NEUROMA NEUROPATHY NEUROSIS NIGHT BLINDNESS NOCTURIA NODAL ARRHYTHMIA NODAL TACHYCARDIA NORMOCYTIC ANEMIA NYSTAGMUS OBESITY OCCLUSION OCULOGYRIC CRISIS OLIGURIA OPHTHALMITIS OPHTHALMOPLEGIA OPISTHOTONOS OPTIC ATROPHY OPTIC NEURITIS ORAL MONILIASIS ORCHITIS OSTEOMALACIA OSTEOMYELITIS OSTEOPOROSIS OSTEOPOROSIS FRACTURE OSTEOSCLEROSIS OTHER MUSCULOSKELETAL DISORDERS OTHER SEXUAL DYSFUNCTION FEMALE OTHER SEXUAL DYSFUNCTION MALE OTITIS EXTERNA OTITIS MEDIA

S75

OVARIAN CARCINOMA OVARIAN CYST OVARIAN DISORDER OVERDOSE OVULATION FAILURE PAIN PAINFUL SWELLING PALLOR PALPITATION PANCARDITIS PANCREATITIS PANCYTOPENIA PAPILLEDEMA PARALYSIS PARANOID REACTION PARAPLEGIA PARATHYROID DISORDER PARESTHESIA PAROSMIA PAROTID GLAND ENLARGEMENT PATENT DUCTUS ARTERIOSUS PATHOLOGICAL FRACTURE PELVIC PAIN PENILE ERECTION PENIS DISORDER PEPTIC ULCER PEPTIC ULCER HEMORRHAGE PERFORATED CORNEAL ULCER PERFORATED PEPTIC ULCER PERFORATED ULCER PERICARDIAL EFFUSION PERICARDITIS PERIODONTAL ABSCESS PERIODONTITIS PERIPHERAL EDEMA PERIPHERAL GANGRENE PERIPHERAL NEURITIS PERIPHERAL VASCULAR DISORDER PERITONITIS PERMANENT DEAFNESS PERSONALITY DISORDER PETECHIA PETECHIAL RASH PHARYNGITIS PHENYLKETONURIA PHLEBITIS

S76

PHOTOPHOBIA PHOTOSENSITIVITY REACTION PILONIDAL CYST PLASMACYTOSIS PLATELET ADHESIVENESS DECREASED PLATELET ADHESIVENESS INCREASED PLEOCYTOSIS PLEURAL EFFUSION PNEUMONIA PNEUMOTHORAX POLYARTERITIS NODOSA POLYCYSTIC KIDNEY POLYCYTHEMIA POLYNEURITIS POLYSEROSITIS POLYURIA PORENCEPHALY PORPHYRIA PORPHYRINURIA POSTMATURE BIRTH POSTPARTUM HEMORRHAGE POSTURAL HYPOTENSION PR INTERVAL PROLONGED PR INTERVAL SHORTENED PREGNANCY DISORDER PREMATURE BIRTH PREMATURE EPIPHYSEAL CLOSURE PRIAPISM PROCTITIS INCREASED PROSTATE NEOPLASIA PROSTATIC CARCINOMA PROSTATIC DISORDER PROSTATIC SPECIFIC ANTIGEN DECREASED PROSTATIC SPECIFIC ANTIGEN INCREASED PROTHROMBIN DECREASED PROTHROMBIN INCREASED PRURITUS PSEUDOMEMBRANOUS COLITIS PSEUDOMEMBRANOUS ENTEROCOLITIS PSORIASIS PSYCHOSIS PSYCHOTIC DEPRESSION PTOSIS PULMONARY ARTERY THROMBOSIS PULMONARY EMBOLUS

S77

PULMONARY HYPERTENSION PULMONARY INFARCT PULMONARY INFILTRATE PULMONARY MYCOSIS PULMONARY THROMBOSIS PULMONIC STENOSIS PUPILLARY DISORDER PURPURA PURPURA FULMINANS PURPURIC RASH PUSTULAR RASH PUSTULES SKIN PYELONEPHRITIS PYLORIC STENOSIS PYOGENIC ARTHRITIS PYURIA QT INTERVAL PROLONGED QT INTERVAL SHORTENED QUADRIPLEGIA RADIATION INJURY RASH REACTIVATED DUODENAL ULCER RECTAL HEMORRHAGE RED MAN'S SYNDROME REFLEXES DECREASED REFLEXES INCREASED REFRACTORY ANEMIA RENAL CARCINOMA RENAL HYPERTENSION RESPIRATORY ACIDOSIS RESPIRATORY ALKALOSIS RESPIRATORY DISORDER RESPIRATORY DISTRESS SYNDROME RESPIRATORY MONILIASIS RESPIRATORY TRACT INFECTION RETICULOENDOTHELIAL BLOCKADE RETICULOENDOTHELIAL HYPERPLASIA RETINAL ARTERY OCCLUSION RETINAL DEGENERATION RETINAL DETACHMENT RETINAL DISORDER RETINAL EDEMA RETINAL HEMORRHAGE RETINAL PIGMENTATION RETINAL VASCULAR DISORDER RETINAL VEIN THROMBOSIS

S78

RETINITIS RETROBULBAR NEURITIS RETROPERITONEAL FIBROSIS RETROPERITONEAL HEMORRHAGE RHEUMATOID ARTHRITIS RHINITIS RUPTURE OF SPLEEN RUPTURED UTERUS SALICYLISM SALIVARY GLAND ENLARGEMENT SALPINGITIS SARCOIDOSIS SARCOMA SCHIZOPHRENIC REACTION SCLERITIS SCLERODERMA SCLEROSING CHOLANGITIS SCROTAL EDEMA SEBORRHEA SEDIMENTATION RATE DECREASED SEDIMENTATION RATE INCREASED SENSORY DISTURBANCE SEPSIS SERUM IRON INCREASED SERUM SICKNESS SGOT INCREASED SGPT INCREASED SHOCK SIALADENITIS SIALOLITHIASIS SINUS BRADYCARDIA SINUSITIS SKIN ATROPHY SKIN CARCINOMA SKIN DISCOLORATION SKIN DISORDER SKIN GRANULOMA SKIN HYPERTROPHY SKIN MELANOMA SKIN NECROSIS SKIN NODULE SKIN STRIAE SKIN ULCER SLEEP DISORDER SMALL INTESTINE PERFORATION SOMNOLENCE

S79

SPASTIC PARALYSIS SPEECH DISORDER SPERMATOGENESIS ARREST SPHEROCYTOSIS SPIDER ANGIOMA SPINA BIFIDA SPLENOMEGALY SPUTUM INCREASED ST DEPRESSED ST ELEVATED STENOSIS OF COLON STENOSIS OF JEJUNUM STEVENS JOHNSON SYNDROME STILLBIRTH STOMACH ATONY STOMACH ULCER STOMATITIS STOOLS LOOSE STRABISMUS STRIDOR STUPOR SUBARACHNOID HEMORRHAGE SUBCUTANEOUS EMPHYSEMA SUBCUTANEOUS NODULE SUBDURAL HEMATOMA SUDDEN DEATH SUDDEN INFANT DEATH SUICIDAL IDEATION SUICIDE ATTEMPT SUICIDE GESTURE SULFHEMOGLOBINEMIA SULFONAMIDE CRYSTALLURIA SUPRAVENTRICULAR EXTRASYSTOLES SUPRAVENTRICULAR TACHYCARDIA SWEATING SWEATING DECREASED SYNCOPE SYNDACTYLY SYNOVITIS T INVERTED TACHYCARDIA TARDIVE DYSKINESIA TASTE LOSS TASTE PERVERSION TEETH GRINDING TENDON DISORDER

S80

TENDON RUPTURE TENESMUS TENOSYNOVITIS TESTICULAR ATROPHY TETANY TETRALOGY OF FALLOT THINKING ABNORMAL THIRST THROMBIN DECREASED THROMBIN INCREASED THROMBOCYTHEMIA THROMBOCYTOPENIA THROMBOCYTOPENIC PURPURA THROMBOPHLEBITIS THROMBOSIS THROMBOTIC THROMBOCYTOPENIC PURPURA THYROID ADENOMA THYROID ATROPHY THYROID CARCINOMA THYROID DISORDER THYROID NEOPLASIA THYROIDITIS TINNITUS TOLERANCE DECREASED TOLERANCE INCREASED TONGUE DISCOLORATION TONGUE DISORDER TONGUE EDEMA TOOTH CARIES TOOTH DISCOLORATION TOOTH DISORDER TORSADES DE POINTES TORTICOLLIS TOXEMIA OF PREGNANCY TOXIC NEPHROPATHY TRANSPOSITION OF GREAT VESSELS TREMOR TRISMUS TUBERCULOSIS AGGRAVATED TUMOR LYSIS SYNDROME TWITCHING ULCERATIVE COLITIS ULCERATIVE ENTEROCOLITIS ULCERATIVE PROCTITIS ULCERATIVE STOMATITIS UNEXPECTED BENEFIT

S81

UNINTENDED PREGNANCY UREA CLEARANCE DECREASED UREMIA UREMIC COMA URETHRAL PAIN URETHRITIS URICACIDURIA URINARY CASTS URINARY FREQUENCY URINARY HESITANCY URINARY INCONTINENCE URINARY RETENTION URINARY TRACT DISORDER URINARY TRACT INFECTION URINARY URGENCY URINE ABNORMALITY UROGENITAL NEOPLASIA UROLITHIASIS URTICARIA UTERINE ATONY UTERINE DISORDER UTERINE ENLARGEMENT UTERINE HEMORRHAGE UTERINE NEOPLASM UTERINE POLYP UTERINE SPASM UTERINE SUBINVOLUTION UVEITIS VAGINAL HEMORRHAGE VAGINAL MONILIASIS VAGINITIS VARICOSE VEIN VASCULAR ANOMALY VASCULAR DISORDER VASCULAR HEADACHE VASCULAR PURPURA VASCULITIS VASOCONSTRICTION VASODILATATION VASOSPASM VASOVAGAL EVENT VENOOCCLUSIVE LIVER DISEASE VENOSPASM VENOUS PRESSURE INCREASED VENTRICULAR ARRHYTHMIA VENTRICULAR EXTRASYSTOLES

S82

VENTRICULAR FIBRILLATION VENTRICULAR SEPTAL DEFECT VENTRICULAR TACHYCARDIA VERTIGO VESICULOBULLOUS RASH VESTIBULAR DISORDER VIREMIA VIRILISM VISUAL FIELD DEFECT VITAMIN TOXICITY VOCAL CORD PARALYSIS VOICE ALTERATION VOMITING VULVOVAGINAL DISORDER VULVOVAGINITIS WATER INTOXICATION WEIGHT GAIN WEIGHT LOSS WITHDRAWAL BLEEDING WITHDRAWAL SYNDROME WORSENING HEART FAILURE WRIST DROP XANTHOMATOSIS YAWN

Supplementary Figure 4: Proteins (Accession Numbers) in network fragments I-IX.

Fragment I

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene ID for Entrez Gene ID for Entrez Gene ID for Gene Symbol Human Mouse Rat ABCB1 5243 18671 170913 ABCC1 4363 17250 24565 ABCC2 1244 12780 25303 ABCG2 9429 26357 312382 ADA 100 11486 24165 ATM 472 11920 300711 BCL2 596 12043 24224 CASP1 834 12362 25166 CASP3 836 12367 25402 CASP8 841 12370 64044 CASP9 842 12371 58918 CD3 CD22 933 12483 308501 CD38 952 12494 25668 CD40 958 21939 171369

S83

CD52 1043 23833 117054 CD33 (includes EG:945) 945 233274 361584 CDKN1B 1027 12576 83571 CHUK 1147 12675 309361 CXCL12 6387 20315 24772 DCK 1633 13178 79127 ESR1 2099 13982 24890 FYN 2534 14360 25150 GRB2 2885 14784 81504 GSTP1 2950 14870|14869 29438|24426 IKBKB 3551 16150 84351 IKBKE 9641 56489 363984 IL11 3589 16156 171040 IL2RA 3559 16184 25704 IL6ST 3572 16195 25205 ITGA5 3678 16402 315346 KIT 3815 16590 64030 KRAS 3845 16653 24525 LCK 3932 16818 313050 LYN 4067 17096 81515 MAF 4094 17132 54267 MPL 4352 17480 366455 MS4A1 931 12482 309217 MYCN 4613 18109 298894 NCAM1 4684 17967 24586 NFE2L2 4780 18024 83619 NFKB1 4790 18033 81736 PARP1 142 11545 25591 PRKCA 5578 18750 24680 RXRA 6256 20181 25271 SHC1 6464 20416 85385 SMPD2 6610 20598 83537 SPN 6693 20737 24796 SRC 6714 20779 83805 STAT3 6774 20848 25125 THY1 7070 21838 24832 TP73 7161 22062 362675

Fragment II

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Symbol Human Mouse Rat ACE 1636 11421 24310 ACHE 43 11423 83817 ADRA1A 148 11549 29412 ADRA1B 147 11548 24173 ADRB1 153 11554 24925

S84

ADRB2 154 11555 24176 ADRBK1 156 110355 25238 ADRBK2 157 320129 25372 AGT 183 11606 24179 AGTR1 185 11607 24180 ARNT2 9915 11864 25243 ATP1A1 476 11928 24211 ATP1B1 481 11931 25650 BDKRB2 624 12062 25245 CREB1 1385 12912 81646 CTNNB1 1499 12387 84353 CXCR4 7852 12767 60628 DDC 1644 13195 24311 DLG4 1742 13385 29495 DRD1 1812 13488 24316 DRD2 1813 13489 24318 EGR1 1958 13653 24330 FN1 2335 14268 25661 GABARAP 11337 56486 58974 GABRA5 2558 110886 29707 GABRB3 2562 14402 24922 GABRG2 2566 14406 29709 GNAS 2778 14683 24896 GRIN1 2902 14810 24408 GRIN2B 2904 14812 24410 GRK4 2868 14772 59077 HRH1 3269 15465 24448 HRH2 3274 15466 25461 HTR4 3360 15562 25324 HTR1A 3350 15550 24473 HTR2A 3356 15558 29595 ID3 3399 15903 25585 JUN 3725 16476 24516 MAOA 4128 17161 29253 MAOB 4129 109731 25750 MAPK1 5594 26413 116590 MITF 4286 17342 25094 MYC 4609 17869 24577 MYOD1 4654 17927 337868 NR3C1 2908 14815 24413 NR3C2 4306 110784 25672 OPRD1 4985 18386 24613 OPRK1 4986 18387 29335 OPRM1 4988 18390 25601 PPP2CA 5515 19052 24672 PREP 5550 19072 83471 PRKCB1 5579 18751 25023 REN 5972 19701 24715 SCN1A 6323 20265 81574 SCNN1B 6338 20277 24767

S85

SLC12A3 6559 20497 54300 SLC6A2 6530 20538 83511 SLC6A3 6531 13162 24898 SLC6A4 6532 15567 25553 SP1 6667 20683 24790 SPI1 6688 20375 366126 SRC 6714 20779 83805 THRB 7068 21834 24831 TPH1 7166 21990 24848 TSPO 706 12257 24230

Fragment III

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Symbol Human Mouse Rat ABCA1 19 11303 313210 APOA1 335 11806 25081 APOB 338 238055 54225 APOE 348 11816 25728 CETP 1071 CRP 1401 12944 25419 GPT 2875 76282 81670 HMGCR 3156 15357 25675 LDLR 3949 16835 300438 LIPC 3990 15450 24538 LPA 4018 LPL 4023 16956 24539 PPARA 5465 19013 25747 PPARG 5468 19016 25664 PRKAA2 5563 108079 78975 SOAT1 6646 20652 81782 SOD2 6648 20656 24787 SP1 6667 20683 24790 SREBF1 6720 20787 78968

Fragment IV

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Entrez Gene ID for Entrez Gene ID for Entrez Gene ID Gene Symbol Human Mouse for Rat ADM 133 11535 25026 Ap1 AR 367 11835 24208 BAX 581 12028 24887 BBC3 27113 170770 317673 BCL2 596 12043 24224 CASP3 836 12367 25402 Caspase

S86

Cbp/p300 CCND1 595 12443 58919 CD4 920 12504 24932 CD34 947 12490 305081 CEACAM1 634 26365 81613 CEACAM5 1048 CEACAM3 (includes EG:1084) 1084 26366 CSF2 1437 12981 116630 DHFR 1719 13361 24312 EGF 1950 13645 25313 EGFR 1956 13649 24329 EPAS1 2034 13819 29452 EPO 2056 13856 24335 ERBB2 2064 13866 24337 ERBB3 2065 13867 29496 Erbb2 dimer F2 2147 14061 29251 FKBP4 2288 14228 260321 FKBP1A 2280 14225 25639 FKBP51-TEBP-GR-HSP90- HSP70 FKBP52-Dyenin-Glucocorticoid- GR-HSP90 Hsp90 IL2 3558 16183 116562 IL6 3569 16193 24498 IL1R1 3554 16177 25663 IL1RAP 3556 16180 25466 JUN 3725 16476 24516 MYC 4609 17869 24577 NFkB NR0B1 190 11614 58850 NR2F2 7026 11819 113984 NR3C1 2908 14815 24413 PGR 5241 18667 25154 PRPF6 24148 68879 366276 PTGES 9536 64292 59103 PTGS1 5742 19224 24693 PTGS2 5743 19225 29527 RB1 5925 19645 24708 RNA polymerase II SELP 6403 20344 25651 SHBG 6462 20415 24775 SP1 6667 20683 24790 TOP2A 7153 21973 360243 TP53 7157 22059 24842 TP73 7161 22062 362675 TUBB4 10382 22153 29213 TUBB2A 7280 22151 498736 TYMS 7298 22171 29261 YY1 7528 22632 24919

S87

Fragment V

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene Entrez Gene ID for Entrez Gene ID for Symbol Human Entrez Gene ID for Mouse Rat Actin ADAM17 6868 11491 57027 AKT1 207 11651 24185 APP 351 11820 54226 BTK 695 12229 367901

Calmodulin CAT 847 12359 24248 CCL2 6347 20293 287562 CCR1 1230 12768 57301 CCR2 1231 12772 60463 DARC 2532 13349 E2F1 1869 13555 399489 FOS 2353 14281 314322 GTF2I 2969 14886 353256 GUSB 2990 110006 24434 Histone h3 Hsp90 ICAM1 3383 15894 25464 IL8 3576 IL-1R

IL1/IL6/TN F IL1A 3552 16175 24493 IL1RN 3557 16181 60582 Itgal-Itgb2 ITGAM 3684 16409 25021 ITGB2 3689 16414 309684 KLF4 9314 16600 114505 KLF11 8462 194655 313994 Mapk MAPK1 5594 26413 116590 MAPK3 5595 26417 50689 MMP9 4318 17395 81687 MPO 4353 17523 303413 MZF1 7593 109889 361508 NFkB NOS1 4842 18125 24598 NOS3 4846 18127 24600 NOS2A 4843 18126 24599 ODC1 4953 18263 24609 PDIA3 2923 14827 29468 PLAT 5327 18791 25692 PLAU 5328 18792 25619

S88

PLG 5340 18815 85253 SELE 6401 20339 25544

20700|20703|20704|20701|2070 SERPINA1 5265 2 24648

SERPINE1 5054 18787 24617 SPHK1 8877 20698 170897 SRC 6714 20779 83805 STAT3 6774 20848 25125 TNF 7124 21926 24835

TNFRSF1A 7132 21937 25625 VCAM1 7412 22329 25361

Fragment VI

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Gene Symbol Human Mouse Rat ARAF 369 11836 64363 CAV1 857 12389 25404 CSK 1445 12988 315707 CTSB 1508 13030 64529 EGR1 1958 13653 24330 ELN 2006 13717 25043 FGF2 2247 14173 54250 GLB1 2720 12091 316033 GRB2 2885 14784 81504 IGF2 3481 16002 24483 Igfbp LAMA3 3909 16774 307582 LAMC2 3918 16782 192362 MAP2K1 5604 26395 170851 Mek1/2 Mmp MMP1 4312 83995 300339 MMP2 4313 17390 81686 MMP3 4314 17392 171045 MMP9 4318 17395 81687 MMP13 4322 17386 171052 NFKB1 4790 18033 81736 PCNA 5111 18538 25737 RAF1 5894 110157 24703 Ras RNA polymerase II STAT3 6774 20848 25125 Tgf beta TGFB1 7040 21803 59086 TGFB2 7042 21808 81809

S89

TNFSF11 8600 21943 117516 VDR 7421 22337 24873

Fragment VII

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Symbol Human Mouse Rat CREBBP 1387 12914 54244 FOS 2353 14281 314322 GHRH 2691 14601 29446 GNRH1 2796 14714 25194 IGF1 3479 16000 24482 NCF2 4688 17970 364018 NR3C1 2908 14815 24413 PRDX6 9588 11758 94167 PSIP1 11168 101739 313323

Fragment VIII

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Gene Symbol Human Mouse Rat ADRB2 154 11555 24176 AVP 551 11998 24221 CALM2 805 12314 50663 Calmodulin CCK 885 12424 25298 CCKAR 886 12425 24889 CCKBR 887 12426 25706 CEBPA 1050 12606 24252 CHAT 1103 12647 290567 COMT 1312 12846 24267 Creb CREBBP 1387 12914 54244 CRH 1392 12918 81648 DBH 1621 13166 25699 EDNRA 1909 13617 24326 ESR1 2099 13982 24890 FOS 2353 14281 314322 GAD1 2571 14415 24379 GAL 51083 14419 29141 GAST 2520 14459 25320 GCG 2641 14526 24952 GPI 2821 14751 292804 GRK5 2869 14773 59075 HDAC1 (includes EG:3065) 3065 433759 297893

S90

Histone h3 INDO 3620 15930 66029 JUN 3725 16476 24516 MIF 4282 17319 81683 MITF 4286 17342 25094 NPPA 4878 230899 24602 NTS 4922 67405 299757 PENK 5179 18619 29237 PLA2 PLA2G2D 26279 18782 298579 POMC 5443 18976 24664 PRKCA 5578 18750 24680 PTH 5741 19226 24694 PTN 5764 19242 24924 RB1 5925 19645 24708 RELA 5970 19697 309165 SCT 6343 20287 24769 SP1 6667 20683 24790 SRC 6714 20779 83805 SST 6750 20604 24797 STAT1 6772 20846 25124 TACR1 6869 21336 24807 TBX2 6909 21385 303398 TCF7L2 6934 21416 679869 TH 7054 21823 25085 TP53 7157 22059 24842 TPO 7173 22018 54314 TRH 7200 22044 25569 TRPV1 7442 193034 83810 TYR 7299 22173 308800 VIPR1 7433 22354 24875 Fragment IX

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Gene Entrez Gene ID for Entrez Gene ID for Entrez Gene ID for Symbol Human Mouse Rat

ADCYAP1R1 117 11517 24167 ADRBK2 157 320129 25372 AVPR2 554 12000 25108 CACNA1B 774 12287 257648 Calmodulin DLG4 1742 13385 29495 DRD1 1812 13488 24316 EDNRB 1910 13618 50672 GNB1 2782 14688 24400 GNB2L1 10399 14694 83427 GRK4 2868 14772 59077 GUCY1A3 2982 60596 497757 GUCY1B3 2983 54195 25202 MYLK 4638 107589 288057 S91

MYOD1 4654 17927 337868 NPPB 4879 18158 25105 NPY 4852 109648 24604 NPY2R 4887 18167 66024 PRKCE 5581 18754 29340 PRKCG 5582 18752 24681 RELA 5970 19697 309165 SRC 6714 20779 83805 TFAP2A 7020 21418 306862 TNNC1 7134 21924 290561

Fragments I-IX

© 2000-2008 Ingenuity Systems, Inc. All rights reserved. Entrez Gene ID Entrez Gene Gene Symbol for Human Entrez Gene ID for Mouse ID for Rat ABCA1 19 11303 313210 ABCB1 5243 18671 170913 ABCC1 4363 17250 24565 ABCC2 1244 12780 25303 ABCG2 9429 26357 312382 ACE 1636 11421 24310 ACHE 43 11423 83817 Actin ADA 100 11486 24165 ADAM17 6868 11491 57027 ADCYAP1R1 117 11517 24167 ADM 133 11535 25026 ADRA1A 148 11549 29412 ADRA1B 147 11548 24173 ADRB1 153 11554 24925 ADRB2 154 11555 24176 ADRBK1 156 110355 25238 ADRBK2 157 320129 25372 AGT 183 11606 24179 AGTR1 185 11607 24180 AKT1 207 11651 24185 Ap1 APOA1 335 11806 25081 APOB 338 238055 54225 APOE 348 11816 25728 APP 351 11820 54226 AR 367 11835 24208 ARAF 369 11836 64363 ARNT2 9915 11864 25243 ATM 472 11920 300711 ATP1A1 476 11928 24211 ATP1B1 481 11931 25650 AVP 551 11998 24221

S92

AVPR2 554 12000 25108 BAX 581 12028 24887 BBC3 27113 170770 317673 BCL2 596 12043 24224 BDKRB2 624 12062 25245 BTK 695 12229 367901 CACNA1B 774 12287 257648 CALM2 805 12314 50663 Calmodulin CASP1 834 12362 25166 CASP3 836 12367 25402 CASP8 841 12370 64044 CASP9 842 12371 58918 Caspase CAT 847 12359 24248 CAV1 857 12389 25404 Cbp/p300 CCK 885 12424 25298 CCKAR 886 12425 24889 CCKBR 887 12426 25706 CCL2 6347 20293 287562 CCND1 595 12443 58919 CCR1 1230 12768 57301 CCR2 1231 12772 60463 CD3 CD4 920 12504 24932 CD22 933 12483 308501 CD34 947 12490 305081 CD38 952 12494 25668 CD40 958 21939 171369 CD52 1043 23833 117054 CD33 (includes EG:945) 945 233274 361584 CDKN1B 1027 12576 83571 CEACAM1 634 26365 81613 CEACAM5 1048 CEACAM3 (includes EG:1084) 1084 26366 CEBPA 1050 12606 24252 CETP 1071 CHAT 1103 12647 290567 CHUK 1147 12675 309361 COMT 1312 12846 24267 Creb CREB1 1385 12912 81646 CREBBP 1387 12914 54244 CRH 1392 12918 81648 CRP 1401 12944 25419 CSF2 1437 12981 116630 CSK 1445 12988 315707 CTNNB1 1499 12387 84353 CTSB 1508 13030 64529 S93

CXCL12 6387 20315 24772 CXCR4 7852 12767 60628 DARC 2532 13349 DBH 1621 13166 25699 DCK 1633 13178 79127 DDC 1644 13195 24311 DHFR 1719 13361 24312 DLG4 1742 13385 29495 DRD1 1812 13488 24316 DRD2 1813 13489 24318 E2F1 1869 13555 399489 EDNRA 1909 13617 24326 EDNRB 1910 13618 50672 EGF 1950 13645 25313 EGFR 1956 13649 24329 EGR1 1958 13653 24330 ELN 2006 13717 25043 EPAS1 2034 13819 29452 EPO 2056 13856 24335 ERBB2 2064 13866 24337 ERBB3 2065 13867 29496 Erbb2 dimer ESR1 2099 13982 24890 F2 2147 14061 29251 FGF2 2247 14173 54250 FKBP4 2288 14228 260321 FKBP1A 2280 14225 25639 FKBP51-TEBP-GR- HSP90-HSP70 FKBP52-Dyenin- Glucocorticoid-GR-HSP90 FN1 2335 14268 25661 FOS 2353 14281 314322 FYN 2534 14360 25150 GABARAP 11337 56486 58974 GABRA5 2558 110886 29707 GABRB3 2562 14402 24922 GABRG2 2566 14406 29709 GAD1 2571 14415 24379 GAL 51083 14419 29141 GAST 2520 14459 25320 GCG 2641 14526 24952 GHRH 2691 14601 29446 GLB1 2720 12091 316033 GNAS 2778 14683 24896 GNB1 2782 14688 24400 GNB2L1 10399 14694 83427 GNRH1 2796 14714 25194 GPI 2821 14751 292804 GPT 2875 76282 81670 GRB2 2885 14784 81504

S94

GRIN1 2902 14810 24408 GRIN2B 2904 14812 24410 GRK4 2868 14772 59077 GRK5 2869 14773 59075 GSTP1 2950 14870|14869 29438|24426 GTF2I 2969 14886 353256 GUCY1A3 2982 60596 497757 GUCY1B3 2983 54195 25202 GUSB 2990 110006 24434 HDAC1 (includes EG:3065) 3065 433759 297893 Histone h3 HMGCR 3156 15357 25675 HRH1 3269 15465 24448 HRH2 3274 15466 25461 Hsp90 HTR4 3360 15562 25324 HTR1A 3350 15550 24473 HTR2A 3356 15558 29595 ICAM1 3383 15894 25464 ID3 3399 15903 25585 IGF1 3479 16000 24482 IGF2 3481 16002 24483 Igfbp IKBKB 3551 16150 84351 IKBKE 9641 56489 363984 IL2 3558 16183 116562 IL6 3569 16193 24498 IL8 3576 IL11 3589 16156 171040 IL-1R IL1/IL6/TNF IL1A 3552 16175 24493 IL1R1 3554 16177 25663 IL1RAP 3556 16180 25466 IL1RN 3557 16181 60582 IL2RA 3559 16184 25704 IL6ST 3572 16195 25205 INDO 3620 15930 66029 ITGA5 3678 16402 315346 Itgal-Itgb2 ITGAM 3684 16409 25021 ITGB2 3689 16414 309684 JUN 3725 16476 24516 KIT 3815 16590 64030 KLF4 9314 16600 114505 KLF11 8462 194655 313994 KRAS 3845 16653 24525 LAMA3 3909 16774 307582 LAMC2 3918 16782 192362 LCK 3932 16818 313050 S95

LDLR 3949 16835 300438 LIPC 3990 15450 24538 LPA 4018 LPL 4023 16956 24539 LYN 4067 17096 81515 MAF 4094 17132 54267 MAOA 4128 17161 29253 MAOB 4129 109731 25750 MAP2K1 5604 26395 170851 Mapk MAPK1 5594 26413 116590 MAPK3 5595 26417 50689 Mek1/2 MIF 4282 17319 81683 MITF 4286 17342 25094 Mmp MMP1 4312 83995 300339 MMP2 4313 17390 81686 MMP3 4314 17392 171045 MMP9 4318 17395 81687 MMP13 4322 17386 171052 MPL 4352 17480 366455 MPO 4353 17523 303413 MS4A1 931 12482 309217 MYC 4609 17869 24577 MYCN 4613 18109 298894 MYLK 4638 107589 288057 MYOD1 4654 17927 337868 MZF1 7593 109889 361508 NCAM1 4684 17967 24586 NCF2 4688 17970 364018 NFE2L2 4780 18024 83619 NFkB NFKB1 4790 18033 81736 NOS1 4842 18125 24598 NOS3 4846 18127 24600 NOS2A 4843 18126 24599 NPPA 4878 230899 24602 NPPB 4879 18158 25105 NPY 4852 109648 24604 NPY2R 4887 18167 66024 NR0B1 190 11614 58850 NR2F2 7026 11819 113984 NR3C1 2908 14815 24413 NR3C2 4306 110784 25672 NTS 4922 67405 299757 ODC1 4953 18263 24609 OPRD1 4985 18386 24613 OPRK1 4986 18387 29335 OPRM1 4988 18390 25601

S96

PARP1 142 11545 25591 PCNA 5111 18538 25737 PDIA3 2923 14827 29468 PENK 5179 18619 29237 PGR 5241 18667 25154 PLA2 PLA2G2D 26279 18782 298579 PLAT 5327 18791 25692 PLAU 5328 18792 25619 PLG 5340 18815 85253 POMC 5443 18976 24664 PPARA 5465 19013 25747 PPARG 5468 19016 25664 PPP2CA 5515 19052 24672 PRDX6 9588 11758 94167 PREP 5550 19072 83471 PRKAA2 5563 108079 78975 PRKCA 5578 18750 24680 PRKCB1 5579 18751 25023 PRKCE 5581 18754 29340 PRKCG 5582 18752 24681 PRPF6 24148 68879 366276 PSIP1 11168 101739 313323 PTGES 9536 64292 59103 PTGS1 5742 19224 24693 PTGS2 5743 19225 29527 PTH 5741 19226 24694 PTN 5764 19242 24924 RAF1 5894 110157 24703 Ras RB1 5925 19645 24708 RELA 5970 19697 309165 REN 5972 19701 24715 RNA polymerase II RXRA 6256 20181 25271 SCN1A 6323 20265 81574 SCNN1B 6338 20277 24767 SCT 6343 20287 24769 SELE 6401 20339 25544 SELP 6403 20344 25651

20700|20703|20704|20701|20 SERPINA1 5265 702 24648 SERPINE1 5054 18787 24617 SHBG 6462 20415 24775 SHC1 6464 20416 85385 SLC12A3 6559 20497 54300 SLC6A2 6530 20538 83511 SLC6A3 6531 13162 24898 SLC6A4 6532 15567 25553 SMPD2 6610 20598 83537 S97

SOAT1 6646 20652 81782 SOD2 6648 20656 24787 SP1 6667 20683 24790 SPHK1 8877 20698 170897 SPI1 6688 20375 366126 SPN 6693 20737 24796 SRC 6714 20779 83805 SREBF1 6720 20787 78968 SST 6750 20604 24797 STAT1 6772 20846 25124 STAT3 6774 20848 25125 TACR1 6869 21336 24807 TBX2 6909 21385 303398 TCF7L2 6934 21416 679869 TFAP2A 7020 21418 306862 Tgf beta TGFB1 7040 21803 59086 TGFB2 7042 21808 81809 TH 7054 21823 25085 THRB 7068 21834 24831 THY1 7070 21838 24832 TNF 7124 21926 24835 TNFRSF1A 7132 21937 25625 TNFSF11 8600 21943 117516 TNNC1 7134 21924 290561 TOP2A 7153 21973 360243 TP53 7157 22059 24842 TP73 7161 22062 362675 TPH1 7166 21990 24848 TPO 7173 22018 54314 TRH 7200 22044 25569 TRPV1 7442 193034 83810 TSPO 706 12257 24230 TUBB4 10382 22153 29213 TUBB2A 7280 22151 498736 TYMS 7298 22171 29261 TYR 7299 22173 308800 VCAM1 7412 22329 25361 VDR 7421 22337 24873 VIPR1 7433 22354 24875 YY1 7528 22632 24919

S98

Supplementary Table 1

Number COSTART effect spectra Protein co-investigation frequency of Medicine identity similarity to Rosiglitazone spectra similarity to Rosiglitazone medicines 71.06 48.16 12 1,2,3,4,5,6,7,8,9,10,11,12 73.41 59.97 6 1,2,3,4,5,6 76.29 61.45 5 1,2,3,4,5 78.21 70.5 4 1,2,3,4 90.17 82.2 3 1,2,3 96.15 97.24 2 1,2

Supplementary Table 2

Medicine Target 1 Rosiglitazone PPARg 2 Glimepiride beta cells 3 Pioglitazone PPARg 4 Fenofibrate PPARα 5 PPARg 6 Simvastatin HMGCoA 7 Metformin glucose productiion 8 Atorvastatin HMGCoA 9 Bezafibrate PPARα 10 Glipizide beta cells 11 Orlistat lipase inhibition 12 Repaglinide ATP K+ channels

S99

S100

S101

S102

S103

S104

S105

S106

S107