SUPPORTING INFORMATION SECTION Drug Effects Viewed From a Signal Transduction Network Perspective Anton F. Fliri,†,‡ William T. Loging§ and Robert A. Volkmann*,†,‡ †Pfizer 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 Proteins (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 Desoximetasone Betamethasone Fludrocortisone Halometasone monohydrate Betamethasone-21-Valerate Fludrocortisone Acetate Flumethasone Pivalate Paramethasone Acetate 6Beta-Hydroxycortisol Hydrocortisone Prednisolone Prednisone Meprednisone Beclomethasone Dipropionate Clobetasol Propionate Clocortolone Pivalate Fluticasone Propionate Mometasone Furoate Loteprednol etabonate Fluocinonide Halcinonide Fluocinolone Acetonide Flurandrenolide Triamcinolone Acetonide 1,3,5(10)-Estratrien-3,17Beta-Diol-6-One 4-Hydroxyestrone 2-Hydroxyestradiol 2-Hydroxyestriol 4-Hydroxyestradiol Estriol 1,3,5(10)-Estratrien-2,3-Diol-17-One 2-Methyl Ether 2-Methoxyestradiol Beta-Estradiol 3-Methyl Ether Mestranol Ethinyl Estradiol 17Beta-Estradiol 17-Hemisuccinate Estradiol Cypionate Estradiol Valerate Equilenin Podocarpic Acid Allopregnanolone S2 Androstanolone Dehydrocholic Acid Ursodiol Terpin Hydrate Alprostadil Dinoprostone Misoprostol Allethrin Triacetin Latanoprost Loxoprofene Quinic Acid Succinic Anhydride Budesonide Digitoxin Mupirocin Mycophenolate Mofetil HCl Lovastatin Simvastatin 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 Medroxyprogesterone Medrysone Enoxolone Oleanolic Acid Desogestrel Gestrinone Gestodene Norgestrel 5-Cholesten-3Beta-Ol-7-One Calcifediol 19-Hydroxyandrost-4-Ene-3,17-Dione Uvaol 17 Alpha-Dihydroequilin S3 Equilin Norethindrone Norethynodrel Testosterone Tibolone Exemestane Dydrogesterone Progesterone Canrenone Spironolactone Chlormadinone Acetate Ethynodiol Diacetate Norethisterone Acetate Melengestrol Acetate Medroxyprogesterone Acetate Megestrol Acetate Nomegestrol 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 Haloprogin Bis(2-Hydroxy-5-Chlorophenyl) Bithionol Dichlorophen Hexachlorophene Diflunisal Flurbiprofen 2-Amino-5-chlorobenzophenone Bupropion HCl S4 Dicofol Plifenate Lindane Mitotane Acemetacin Indomethacin Cerivastatin Fluvastatin Montelukast Sodium 1,5-Isoquinolinediol 5,7-Dichlorokynurenic Acid Fenarimol Metyrapone FPL 64176 Bisacodyl Papaverine HCl RG-13022 Ethacrynic Acid Butylparaben Ethylparaben Gemfibrozil Octyl Salicylate Ethyl 2-Cyano-3,3-Diphenylacrylate Dienestrol Diethylstilbestrol Chlorotrianisene Dienestrol Diacetate Phenothrin Enterodiol Monobenzone Nabumetone Citrinin Dehydroacetic Acid Dithianon 1,4-Benzoquinone Menadione Phenindione Benzoyl Peroxide Ketoprofen Mandelic Acid Pyromellitic Acid Ibuprofen Niacin S5 2-Tert-Butyl-4-Hydroxyanisole 3-tert-Butyl-4-hydroxyanisole Guaiacol Propofol Probucol 2,2'-Dihydroxy-4,4'-Dimethoxybenzophenone Oxybenzone Erbstatin Analog Fenoprofen Sodium Methylparaben Naproxen Aspirin Diacerein Triflusal Aloe-Emodin Emodin Butein Isoliquiritigenin Phloretin Resorcinol Salicylic Acid Aurintricarboxylic Acid Salsalate Trisalicylic Acid Aurothioglucose Amygdalin Trihydrate Arbutin Guaifenesin Aloin Mangiferin Diosmin Rutin Aflatoxin B1 Aflatoxin G1 Etoposide Teniposide PD-0156707-0015 Podophyllotoxin Cromolyn Sodium Dicumarol Coumestrol Methoxsalen Gallocatechin Gallate, (-)- S6 Gossypetin Kaempferol Hematein PCO 400 O-Cresolphthalein Phenolphthalein Bromadiolon Coumachlor Warfarin Phenprocoumon Amifostine CGP 35348 Alendronate Sodium Pamidronate Ibandronate sodium Carmustine Deferoxamine Mesylate Ifosfamide Busulphan Acamprosate Calcium Mesna Sodium 0155098-0000 Modafinil Omethoate Coumaphos Chlorpyriphos-Methyl Fenchlorphos Leptophos Profenofos Bromfenvinphos Tetrachlorvinphos Fensulfothion Isomalathion Tetraethyl Pyrophosphate Phorate 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 Acetanilide Phenacetin Benzocaine Butamben Methyl Anthranilate Exalamide Mexiletine HCl 4-(N-[3-Chlorophenyl]-Carbamoyloxy)-2-Butynyltrimethylammonium Chloride Barban PF-02543547-00 Felbamate Meprobamate Fenoxycarb Metaxalone Racecadotril Fluvoxamine Maleate Gabexate Mesylate Pentamidine Isethionate Baclofen Cetraxate HCl Gabapentin 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 Aceclofenac Diclofenac Sodium Iodipamide Ipodate Sodium Flufenamic Acid Niflumic Acid Chloramphenicol Chloramphenicol Palmitate Iohexol Iopamidol Metrizamide Efavirenz 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 Minocycline HCl Oxytetracycline Novobiocin Carbidopa Levodopa Methyldopa Metyrosine Liothyronine S9 Aminosalicylic Acid Mesalamine m-Aminophenol Salicylamide Levonordefrin Metaraminol L-Bitartrate Pseudoephedrine HCl Tyrphostin 51 Tyrphostin A9 Tyrphostin AG 879 Capsazepine A-77636 HCl Fenoldopam Dihydrexidine HCl Norapomorphine HBr, R(-)- Nebivolol, hydrochloride Paroxetine 2-Methyl-5-Hydroxytryptamine Maleate BW 723C86 HCl Oxitriptan 6-Chloromelatonin Melatonin CP-099994-01 Primaquine Phosphate Tegaserod Maleate Atomoxetine HCl Nisoxetine HCl Fluoxetine HCl Bifemelane Methoctramine TetraHCl Propafenone HCl Maprotiline HCl Nortriptyline HCl Protriptyline HCl Acebutolol HCl Atenolol Carteolol HCl Formoterol Fumarate DiH2O UK-538348-40 Procaterol HCl Benserazide HCl Midodrine HCl SC-39566A S10 Capsaicin Dihydrocapsaicin Flecainide Acetate Rolipram Troxipide Anisomycin Carvedilol Isamoltane Hemifumarate Bopindolol Malonate Pindolol Propranolol HCl Betaxolol HCl Metoprolol Fumarate Oxprenolol HCl Levobunolol HCl Nadolol Penbutolol Sulfate CP-114271 BRL 37344 Sodium Fenoterol HBr UK-519218-02 Albuterol Terbutaline Sulfate Epinephrine L-Bitartrate Phenylephrine HCl Isoproterenol HCl Norepinephrine L-Bitartrate Clenbuterol HCl Tulobuterol HCl Suloctidil Deflazacort Docetaxel Paclitaxel Amphotericin B Nystatin Mepartricin A Aclarubicin HCl Azithromycin Clarithromycin Erythromycin Josamycin Dirithromycin Roxithromycin S11 Rapamycin Tacrolimus 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 Guanabenz Acetate M-Iodobenzylguanidine Hemisulfate Salt Phenformin HCl 5-(N-Ethyl-N-Isopropyl)-Amiloride Amiloride HCl Phenamil Methanesulfonate Anilazine Irsogladine Maleate Lamotrigine WY-14643 10, 11-Epoxy Carbamazepine Carbamazepine Oxcarbazepine 3,4,4'-Trichlorocarbanilide Diflubenzuron Guanfacine HCl Phenacemide Acetohydroxamic Acid Hydroxyurea Zileuton 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 Albendazole Parbendazole Mebendazole Cycloserine Isocarboxazid Leflunomide Isradipine NVP-ABE-171 5-Phenylhydantoin Phenytoin Pemoline 0119307-0015 PD-0136095-0002 Siguazodan Zardaverine CP-057915 Fluorouracil Carmofur Uracil Mustard Amobarbital Pentobarbital Secobarbital Mephobarbital Phenobarbital Primidone 5-Nitro-6,7-Dichloro-1,4-Dihydro-2,3-Quinoxalinedione Flutamide Acenocoumarol 5,5'-Dithiobis(2-Nitrobenzoic Acid) 3,5-Dinitrocatechol Ro 41-0960 Niclosamide Nifuroxazide S13 Nitrofurazone 1,1'-Trimethylenebis[4-(Hydroxyiminomethyl)Pyridinium Bromide Asoxime Chloride Pralidoxime Chloride 0151832-0042 NO-711 HCl Oxyphencyclimine HCl Furaltadone Furazolidone Nitrofurantoin Molsidomine Oxadixyl Etanidazole N-Benzyl-2-Nitro-1 H-Imidazole-1-Acetamide Ornidazole Secnidazole Oxamniquine Quipazine, 6-Nitro-, Maleate Amlodipine Maleate Salt Diethyl 1,4-Dihydro-2,6-Dimethyl-3,5-Pyridinedicarboxylate Felodipine Lacidipine Methyl 2-(Phenylthio)Ethyl 1,4-Dihydro-2,4,6-Trimethylpyridine-3,5- Dicarboxylate Nicardipine HCl Nifedipine Nisoldipine Nitrendipine Chlordiazepoxide HCl Flunitrazepam Clonazepam Nitrazepam Bromazepam Desalkylflurazepam Nordazepam 1-(2-Chlorophenyl)-N-Methyl-N-(1-Methylpropyl)-3-Isoquinolinecarboxamide