Aβ Peptide Formation 478–480 Abl Inhibitor Lapatinib 47 Acetazolamide 255 Acetylcholinesterase Inhibitors

509

Index a 4-(aminoalkoxy)benzylamines 262 Aβ peptide formation 478–480 aminobenzimidazoles 295–298 Abl inhibitor lapatinib 47 2-(4-aminophenoxy)naphthalene- acetazolamide 255 1,4-dione 140 acetylcholinesterase inhibitors 3-aminoquinazolinediones 7 core (AChEI) 256 scaffold 438 Acquired immune deficiency syndrome amoxapine 62–63 (AIDS) 15 amyloid cascade hypothesis 480 active pharmaceutical ingredients amyloid plaques (APIs) 104–105 Aβ peptide formation 478–480 activity-based protein profiling aggregation 480 (ABPP) 317 amyloid precursor protein (APP) 183 activity landscape modeling (ALM) ANAVEX1–41 498 19, 166 ANAVEX2–73 498 adenosine A2A receptor and adenosine ANAVEX3–71 (AF710B) 501 transporter 292–295 angiotensin converting enzyme (ACE) adenylosuccinate lyase (ASL/ADSL) 262, 415 317 angiotensin II (AII) 369 adverse drug reactions (ADRs) 8 angiotensin II type 1 (AT1)receptor afatinib 48 activity pathway 387–388 affinity purification-based MS (AP-MS) antagonist/PPARγ 377 approach 317 antagonists 372, 377 see also aldose reductase-related protein 2, angiotensin receptor blockers 317 (ARBs) allosteric SMKIs 47–48 antioxidant agents 384–386 α-carbonic anhydrase (CA) 161, 255 endothelins (ET) 372 Alzheimer’s disease 259 NO agents 382 amyloid cascade hypothesis structure of 370–372 480–481 angiotensin receptor blockers (ARBs) amyloid plaques 478–480 369, 372 metal toxicity 481–483 antihypertensive effects of 382 neurofibrillary tangles 481, 482 AT1 receptor 370 neuroinflammation 481–483 binding mode, AT1 372 oxidative stress 481–483 telmisartan 377 AMI-5 11

Drug Selectivity: An Evolving Concept in Medicinal Chemistry, First Edition. Edited by Norbert Handler and Helmut Buschmann. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 510 Index

angiotensin II receptor blockers (ARBs) 11β-hydroxysteroid dehydrogenase PPARγ agonists 415 type 1 (11β-HSD1) 423 6-anilinouracils (6-AUs) 461 β-ketoacyl-acyl carrier protein animal-based screening 80 (ACP) 454 antagonist see proliferator-activated β-lactam antibiotic 434 receptor-γ (PPARγ) β-lactam-fluoroquinolone hybrid

AT1 377–382 molecules 458 ETA receptor 373 bicyclic diamines 450 antibacterial drugs 464–465 Bio Assay Ontology (BAO) 248 antibody/protein drug conjugates bioactivity data sources 248 brentuximab vedotin 219 Bio-Plex Pro magnetic cell signaling chances and challenges 218–219 assays 318 coltuximab ravtansine 222 blood–brain barrier (BBB) 60 effective therapeutic options 223 boronic acid-based glembatumumab vedotin 221 penicillin-binding-protein indatuximab ravtansine 222 inhibitors 452

inotuzumab ozogamicin 221 bradykinin B1 and B2 receptors lorvotuzumab mertansine 222 290–292 trastuzumab emtansine 220 breast cancer brain metastasis 59–62 antidepressant drugs 340–347 brentuximab vedotin 219 antinociceptive multitarget drugs 188 c antioxidant agents 384–386, 485 cancer proteins 60 antitarget receptors 10 cancer signaling bridge (CSB) 60 anti-trypanosomatid MTDL caproctamine 491 combined target/targeting approach cardiovascular diseases 262–264 149–151 catechol-O-methyltransferase (COMT) drug targeting approach 146–149 inhibitors 258 phenotypic approach 138–141 cathepsin-L (CatL) inhibitor 254 target-based approach 141, 143, 146 Cavbase 162 AP5346 (Pro-Lindac) 228 celecoxib 162 approved kinase inhibitors 36, 43–45, cell-based screening 80–81 48 cell phenotypic assays 3-AQD scaffold 439 high content imaging assays arylboronic acids 301–304 323–324 label-free cell phenotypic assays AT1/ETA receptor 374, 375 automated patch clamping 318 324–326 7-azaindole scaffold 165 reporter gene assays 322 cellular assays b automated patch clamping 318 BACE1 inhibitors/metal chelators chemogenomics-based assays 497–498 320–321 bacterialβ-glucuronidase (GUS) enzyme chemoproteomics-based assays 62 315–317 bacterial topoisomerases inhibitors 435 drug discovery 314–321 benextramine 491 high content imaging assays β-amyloid (Aβ) peptides 483 323–324 Index 511

label-free cell phenotypic assays Connectivity Map (cMap) 88 324–326 covalent inhibitors 48 ligand binding assays 314–315 covalent SMKIs 49 miniaturization 313 COX inhibitors 421–422 perspectives 326, 327 COX-2/sEH dual inhibitors 269 protein–protein interaction assays Critical Path initiative 107 319 crystallography/SAR 166–168 protein trafficking assays 319–320 cyclic guanosine monophosphate reporter gene assays 322 (cGMP) 382 signaling assays 317–318 cyclic nucleotide phosphodiesterases 3D organotypic culture 313 (PDEs) 163 cell viability assays 80 cyclooxygenase 2 (COX-2) 216 cephalosporin-based hybrid molecules 457–459 d cephalosporin-fluoroquinolones hybrid dabrafenib 45 molecules 457 Danish University Antidepressant cerulenin 454 Group (DUAG) 337 Chagas’ disease 137 dapoxetine 57–58 ChEMBL 248 dasatinib 59–62 chemical proteomics approach 140 depression 261–262 chemogenomics 16–18 diabetes and related metabolic diseases chemogenomics-based assays 264–267 320–321 1,4-disubstituted aromatic piperidines chemoinformatics 83–84 172 chemoproteomics-based assays disulfide linked drug conjugates 232 315–317 DNA-dependent protein kinase chiral drugs 111 (DNA-PK) 173 8-(3-chlorostyryl) caffeine 259 DNA gyrase 435 chronic myelogenous leukemia (CML) DNA topoisomerase inhibitors 435 112 DNA topoisomerase IV 435 ciprofloxacin 437, 445, 460 docking 82–83 cleavable linkers 231 doctor and patient 115–116 cobimetinib 47 donecopride 486 coltuximab ravtansine 222 dopamine type 2 (D2) antagonist 249 combinations of drugs 12 dopamine type 4 (D4) antagonist 249 competent patient 116 drug conjugates compound promiscuity 4 antibody/protein 217–223 computational and systematic drug enhanced permeation and retention repositioning 234 methods based on genome-wide linker chemistry 229–233 association study 66 polymer 223–229 methods based on knowledge of side preclinical and clinical development effects 64–65 208 methods based on transcriptomics small molecule 209 data 65–66 targeted delivery 209, 233 Computational Conformer Selection therapeutic efficacy 233 (CSS) approach 84 therapeutic opportunities 235 512 Index

drug discovery dual COX-2/LTA4H inhibitor 268 anti-trypanosomatid MTDL, see dual FMS/KIT kinase inhibitors 165 anti-trypanosomatid MTDL dual GPR119 and DPP-IV MML 267

concept of selectivity 151 dual H3 and SERT modulator 263 GPCRs 135 dual HDAC and IMPDH inhibitors neglected tropical diseases (NTDs) 253 136–138, 143 dual MMP-1/CatL inhibitors 254 one-molecule-one-target paradigm dual MMP-2/CA IX inhibitors 255

136 dual NK1 receptor antagonist 262 drug repositioning dual pharmacophores amoxapine 62–63 cephalosporin-based hybrid computational and systematic molecules 457–459 64–68 fluoroquinolizine–rifamycin hybrid dapoxetine 57–58 drugs 462 dasatinib 59–62 fluoroquinolone–aminouracil hybrid duloxetine 58–59 drugs 461–462 list of repositioned drug 56, 57 fluoroquinolone–oxazolidinone perspective 68, 73 hybrid drugs 459–461 sildenafil 58 limitations and perspectives 463–464 sunitinib 59–62 dual phosphoinositide 3-kinase (PI3K)/ thalidomide 59 mammalian target of rapamycin drug repurposing 11 (mTOR) inhibitor 43 animal-based screening 80 dual PI3K/Tyr kinase inhibitors 167 cell-based screening 80–81 dual SERT and 5-HT1A modulator 261 chemoinformatics 83–84 dual TS/DHFR inhibitors 179 docking 82–83 duloxetine 58–59 drug-and protein-centric approach 86 mining of big data 88–89 e network pharmacology 86–88 EC0746 211 protein binding site 84–86 electroconvulsive therapy (ECT) 337 target-based screening 81–82 electronic health 115 drug selectivity 113–114 electronic medical records drug targeting 146–149 (EMRs) 82 druggable enzymes 434 endothelial dysfunction 384 DrugMap Central 87 endothelial growth factor (EGFR) DU-125530 351 inhibitor imatinib 46, 47 endothelin-A receptor (ET ) dual A2A and MAO-B inhibitor 260 A dual acetylcholinesterase antagonists 264 inhibitors-histamine H3 receptor endothelin (ET) receptor 372 antagonists 297–299 AT1 receptor 373 dual AChE and MAO-B inhibitors 258 Merck AII antagonist 372 dual AChEI and AChEI-induced SHR 375 beta-amyloid aggregation 257 DARAs 373, 374 dual-action receptor antagonist enzymatically cleavable linkers 232 (DARAs) 373, 375 E-pharmacophore based virtual dual aromatase–STS inhibitor 252 screening 299–301 Index 513 epigenetic relevant chemical space Gram-negative ParE 449 (ERCS) 14–15 green fluorescent protein (GFP) 319 epigenetics 13–14 GSK2140944 444 erythema nodosum laprosum (ENL) GyrA amino acids 443 59 GyrA/ParC antibacterials 445 eukaryotic SMKIs 38 GyrB/ParE inhibitors 446 EZN-2208 228 Gyrase/topoIV ATPase inhibition and antibacterial activity 447 f farnesoid X receptor (FXR) 299 h FDA-approved inhibitors 44 haptophore 147 flibanserin 347 hCB2R ligands 295–297 fluoroquinolizine–rifamycin hybrid high confidence protein pathways drugs 462 (HCPP) 60 fluoroquinolone–aminouracil hybrid high content imaging assays 323, 324 drugs 461–462 high content screening (HCS) 323 fluoroquinolone–oxazolidinone hybrid histamine H3 receptor antagonists drugs 459–461 262 fluoxetine (Prozac) 58 histone deacetylases (HDACs) 252 folate receptor (FR) positive HLA20 485 cells 211 HLA20A 485 form fits function 83 5-HT1F receptor 356 forward pharmacology 79 5-HT2A receptors 345 fragment-based drug design 250 antagonist 349 frequently used linkers 231 inhibition 345 5-HT6 receptor 356 g human acetylcholinesterase γ-secretase and PPARγ 496–497 (hAChE) 485 GAPDH 143 human African trypanosomiasis gefitinib 46 (HAT) 136 gene surgery 109 human AT1 receptor 370 gene therapy 108–110 human butyrylcholinesterase Generally Recognized as (huBChE) 485 Safe (GRAS) human dihydrofolate reductase compounds 14 (hDHFR) 250 molecules 14 human ether-a-go-go related gene glembatumumab vedotin 221 (hERG)) 349 glufosfamide 214 human immunodeficiency virus glycopeptide-β-lactam hybrid molecules (HIV) 15 458 human thymidylate synthase glycosomal glyceraldehyde-3-phosphate (hTS) 250 dehydrogenase (TbGAPDH) hydrazone based linkers 231 140 hydrophobic interactions 372 glycosomal glycerol kinase (TbGK) hydroxyisoquinolone 437 140 3-hydroxyquinazoline-2,4-dione scaffold G protein-coupled receptors (GPCRs) 438 135, 315, 349 5-hydroxytryptamine (5-HT) 339 514 Index

i linked fluoroquinolone-flavonoid ibrutinib 48 hybrids 285, 286 idebenone 493 linker chemistry idelalisib 48 demands 229–231 imatinib 46, 161 types 231–233 imidazopyridone 379 lipid kinase inhibitor 48 in vitro receptor 346 lorvotuzumab mertansine 222 in vivo testing 12–13 lovastatin 323 indatuximab ravtansine 222 L-type calcium channel 387 individualized medicines 110–112 inflammation and pain 267–269 m Innovative Medicines Initiative (IMI) machine learning 171–173 107 macrolide kinase inhibitors 33 inosine monophosphate dehydrogenase major depressive disorder (MDD) 337 (IMPDH) inhibitors 252 MANTRA 88 inotuzumab ozogamicin 221 MAO-B inhibitor rasagiline 258 irinotecan (CPT-11) 62 MAO inhibitors 486 isoniazid 454 mass spectrometry-based proteomics isothiazoloquinolones (ITQs) 436, 437 techniques 316 master key compound 5–8, 10 k matrix metalloproteases (MMPs) 254 Kaplan–Meier survival analysis 60 MC 1095, 486 kinase inhibitors 8, 9 medium level innovation 114, 115 kinase profiling 38–40 melanin-concentrating hormone receptor 1 (MCH1 receptor) 162 l melarsoprol 137 label-free biosensor techniques 324 merged multiple-ligands (MMLs) label-free cell phenotypic assays Alzheimer’s disease 259 324–326 bioactivity data sources 248 ladostigil (TV-3,326) 495 cardiovascular diseases 262–264 lapachol 139 depression 261–262 lapatinib 46 diabetes and related metabolic leishmaniasis 137 diseases 264–267 ligand-based approaches fragment-based drug design 250 fragment-based approach 180 inflammation and pain 267–269 fragment-based drug discovery network pharmacology 247 strategy 170–171 neurodegenerative diseases 255–256 machine learning 171–173 oncology 251–255 mining literature data 183–186 Parkinson’s disease 260 pharmacophore-based approach polypharmacology 248–249 176–180, 181 protein crystal structures 250–251 SAR around a lead 173–176 QSAR models 249–250 ligand-based pharmacophore modelling rational design of 247 276–278 meta-chlorophenylpiperazine (m-CPP) ligand binding assays 314–315 345 ligand binding domain (LBD) 378 metal chelators 485–486 linezolid 460 metal toxicity 481–483 Index 515 mianserin 346 multitarget drug design miltefosine 137 advanced clinical trials 190 mining literature data 183–186 crystallography/SAR 166–168 mirtazapine 346, 347 ligand-based approaches, see mitogen-activated protein kinase 2 ligand-based approaches (MAP4K2) 304–306 fragment-based approach 163–166 M2 muscarinic receptor inhibitors molecular docking 167–169 491–492 phenotypic assays 186–189 molecular docking 167–169 multitarget 5-HT1A/SERT inhibitors monoamine oxidase (MAO) inhibitors 182 256 multitarget MCH-1 antagonist/DPP-IV monoamine oxidase inhibitors inhibitors 181 (MAOIs) 337 MurD and MurE ligases 453 moxifloxacin 435, 436 Mur ligase inhibitors 453 multi-drug resistance (MDR) muscarinic and σ1 receptors 498–501 proteins 215 mycophenolic acid (MPA) 252 multi-inhibitors 40 multiple ligands 283–285 n multiple myeloma 59 N-acetylglucosamine poly-ethylene multiplicity of action 433 glycol 227 multitarget antiinflammatory N-linked aminopiperidine inhibitors drugs 169 444 multi-target directed ligands N-phenylquinazolin-4-amine hybrids (MTDLs) 138, 478 286–287 acetylcholinesterase (AChE) N1,N8-bisglutathionylspermidine 144 inhibition NAD(P)H:quinone oxidoreductase 162 antioxidants 485 NanoLuc luciferase 315 catalyticactivesite 483 naphthoquinones 139 complex pharmacological profile naphtoquinone-and anthraquinone- 492–496 derived library 140 MAO inhibitors 486 Natural Language Processing (NLP) metal chelators 485–486 techniques 89 M2 muscarinic receptor inhibitors NBTI 5463, 445 491–492 neglected tropical diseases (NTDs) NP-61 483 136–138 peripheral anionic site 483 neprilysin see neutral endopeptidase serotonin 5-HT4 receptor agonist (NEP) 387 486–491 network pharmacology 86–88 treatment of AD neurodegenerative diseases 255–256 BACE1 inhibitors/metal chelators neurofibrillary tangles 481, 482 497–498 neuroinflammation 481–483 γ-secretase and PPARγ 496–497 neurokinin-1 292, 293 muscarinic and σ1receptors neurokinin NK-1 receptor antagonists 498–501 261 multi-target vs. target-specific drugs neutral endopeptidase (NEP) 262, 387 master key compound 5–8, 10 new chemical entities (NCEs) 348–349 safety panels 8–10 new molecular entities (NMEs) 82 516 Index

nifurtimox 137 peroxisome proliferator-activated nilotinib 161 receptors (PPARs) 377 99mTc based conjugate 214 activities 415 nitric oxide (NO) agents approved drugs 415, 416

AT1 receptor 382–384 ARBs 415 cGMP 382, 383 11β-HSD1 423 vasorelaxing effects 383 COX inhibitors 421 non-benzodiazepine alternative 345 dual agonists 404–414 non-cleavable linkers 233 nuclear receptor 397 non-covalent type I and type II SMKIs PPARα 399 42, 45–47 PPAR𝛿 400 (non-fluoroquinolone) dual inhibitors PPARγ 400 439–445 PTP1B 423 non-selective cytochrome P450 subtypes 399, 404, 405 inhibitor 345 personalized medicine non-serotonin transporter (non-SERT) APIs 104–105 338 competent patient 116 non-SERT, phase 2/3 355–356 doctor and patient 115–116 non-steroidal anti-inflammatory drugs drug selectivity 113–114 (NSAIDs) 421 electronic health 115 norepinephrine transporter (NET) 340 gene therapy 108–110 norfloxacin 216 individualized medicines 110–112 novobiocin 446 medium level innovation 114, 115 patient in the focus of research 107 o personalized therapy 107–108 obsessive compulsive disorder (OCD) regenerative medicine 110 345 roots of 103 omapatrilat 263 stratified medicines 112–113 oncology 251–255 systems pharmacology 105–106 one-molecule-one-target paradigm 136 personalized therapy 107–108 osimertinib 48 pharmacophore oxazolidinone–fluoroquinolone hybrid adenosine A2A receptor and molecules 461 adenosine transporter oxidative stress 384, 481–483 292–295 aminobenzimidazoles 295–298 p arylboronic acids 301–304 paclitaxel poliglumex 226 basic framework 276

pan assay interference compounds bradykinin B1 and B2 receptors, (PAINS) 4 290–292 pan-inhibitors 40 computational chemistry 275 Parkinson’s disease 260, 501–502 definition 275 pathological chaperone 256 de novo design 280–281 penicillin-binding proteins (PBPs) 451, discovery of multiple ligands 457 283–285 peptidoglycan biosynthesis 451–454 dual acetylcholinesterase inhibitors- peripheral dopa decarboxylase histamine H3 receptor inhibitors 258 antagonists 297–299 Index 517

E-pharmacophore based virtual combinations of drugs 12 screening 299 compound promiscuity 4 ligand-based method 275–278 data mining 20 limitations 282–283 description 3 linked fluoroquinolone-flavonoid drug repurposing 11, 20 hybrids 285, 286 dual-face 5 mitogen-activated protein kinase 2 epigenetics 13–14 (MAP4K2) 304–306 fingerprints 21 N-phenylquinazolin-4-amine hybrids HIV-infections 15 286–287 in vivo testing 12–13 neurokinin-1 292, 293 PAINS 4 phospholipase A2 and human leuco- polypharmacy 4 triene A4 hydrolase 287–290 promiscuity 4 structure-based method 275, proteochemometric modeling 19 278–279 structure multiple-activity TGFβ-activated kinase 1, 304–306 relationships 17–19 virtual screening 84, 279–280 systems pharmacology 21 pharmacophore-based approach target fishing 19–20 176–181 polypharmacy 4 phenotypic assays 186–189 polysomnographic (PSG) effects 347 2-phenoxy-1,4-naphtoquinone 139 post-biotech pharma 112 phosphodiesterase-5 (PDE5) inhibitor PPARα 399, 401 58 PPAR𝛿 400 phosphoinositide-3-kinase(PI3K)/ PPAR𝛿/β 400 tyrosine kinases dual inhibitors PPARγ 400, 401 166 prokaryotic kinase inhibitors 38 phospholipase A2 and human leuco- proliferator-activated receptor-γ triene A4 hydrolase 287–290 (PPARγ) photosensitizers 216 antagonism 377

PI103 175 AT1 antagonist 378 PI3K/mTOR dual inhibitors 175 AT1 receptor 377 PI3Kinase-related kinase (PIKK) 173 crystal structure of 379 pimavanserin 355 imidazopyridone 379 platelet-derived growth factor receptor LBD 378 (PDGFR) 38 ZDF 379 platencin 454 promiscuity 4 platensimycin 456 promiscuous inhibitors 40 Plexxikon kinase inhibitors 165 prostate specific membrane antigen poly-L-glutamate camptothecin 227 (PSMA) 214 polymer-drug conjugates protein binding site 84–86 chances and challenges 223–225 protein crystal structures 250–251 examples 226–229 protein data bank (PDB) 248 polypharmacology 248, 249, 315 protein–protein interactions (PPIs) 88, charting the epigenetic relevant 319 chemical space 14–15 protein traffic disorders 319 chemical wilderness 4 protein trafficking assays 319–320 chemogenomics 16–18 protein translocation 320 518 Index

protein tyrosine phosphatase 1B selumetinib 43 (PTP1B) 423 serotonergic antidepressants proteochemometric (PCM) modeling clinical experiments 19 5-HT transporter-based multiple PSN-602 267 ligands 337

PubChem BioAssay 248 SSRIs and 5-HT1A Pyrazolopyridine 380 agonists/antagonists 350–352

pyrimidoindoles 451 SSRIs and 5-HT2A receptor pyrrolopyrimidines 449 352–355 multiple serotonergic mechanisms q trazodone 343 quantitative structure activity vilazodone 343 relationships (QSAR) models vortioxetine 343 249–250 NET 340 quercetin 174 non-SERT, phase 2/3 355–356 quinolones 435 serotonergic compounds 347–348 quinolyl propyl piperidine (QPP) SERT 339–340 scaffold 439, 440 SSRI improvement 338–339 quinone-coumarin hybrids 146 serotonin antagonist-reuptake inhibitor (SARI) 343 r serotonin 5-HT4 receptor agonist radioisotope-labeled ATP 40 486–491 receptor antagonists 372 serotonin-reuptake inhibitor (SSRI) 57 reduced folate carrier (RFC) 211 serotonin transporter (SERT) see regenerative medicine 110 selective serotonin reuptake renal antihypertensive rats (RHR) inhibitors (SSRIs) 376 signaling assays 317–318 renin-angiotensin-aldosterone system sildenafil 58 (RAAS) 369 similarity ensemble approach (SEA) renin/angiotensin system (RAS) 415 249 reporter gene assays 322 single pharmacophore molecules representative GSK NBTIs 442 bacterial DNA gyrase and rhinovirus (RHV) coat protein 85 topoisomerase IV 434–451 rifamycin 462 peptidoglycan biosynthesis 451–454 Robalzotan 261, 351 type II fatty acid synthases 454–456 ruxolitinib 47 small molecule drug conjugates chances and challenges 209–210 s examples 210–217 safety panels 8–10 small-molecule kinase inhibitors Sartans 415 (SMKIs) selective MAO-B inhibitors 258 approved, 36, 43–45 48 selective optimization of side activities definition and quantification of (SOSA) 162 selectivity levels, selective serotonin reuptake inhibitors 40–43 (SSRIs) 337–339 kinase profiling, 38–40 DUAG comparisons of clomipramine macrolide 33 338 prokaryotic 38 Index 519

selective 40 trametinib 47 unexplored chemical spaces 49 trastuzumab emtansine 220 small molecule STAT-3 SH2 inhibitors trazodone 343 162 triclosan 454 soluble Epoxide Hydrolase (sEH) 250 tricyclic antidepressants (TCAs) 337, sorafenib 170 340 S. pneumoniae ParC 439 TriTryp genome 142 S. pneumoniae topoIV 438 trivalent drug conjugate EC0225 211 spontaneously hypertensive rat (SHR) TROLOXTM 485 model 375 Trypanosomatidae 147 staurosporine 41, 43 trypanosomatid enzymes 142 steroid sulfatase (STS) enzyme 251 type II fatty acid synthases 454–456 STI-571 165 type II inhibitor gefitinib 45 3D stochastic optical reconstruction type II inhibitor imatinib 45 microscopy (3D STORM) 319 type III allosteric mitogen-activated stratified medicines 112–113 protein kinase stress urinary incontinence (SUI) (MAPK)/extracellular 58–59 signal-regulated kinase (ERK) structure-activity similarity (SAS) maps kinase 43 19 tyrosine kinase inhibitors (TKIs) 112, structure-based pharmacophore 161 modelling 278–279 sunitinib 59–62 u synthetic flavone LY294002 173 UDP-MurNAc 452 systems pharmacology 21, 105–106 UDP-N-acetylmuramoyl (UDP-MurNAc)-pentapeptide t (Park’s nucleotide) 452 Takeda G-protein coupled recptor-5 United States Food and Drug (TGR-5) 299 Administration (FDA) 337 target-based screening 81–82 targeted drugs 138 v target fishing 19–20 vancomycin 458 TCA clomipramine 340 vandetanib 186 T-cell lymphoma. Topoisomerase I vemurafenib 45, 165 (TopoI) 252 vilazodone 343 telmisartan 377, 415 Vintafolide 211 tetrahydropyran (THP)-based dual virtual screening 279–280 topoisomerase inhibitors 442 VisANT 87 TGFβ-activated kinase 1 (TAK1) vortioxetine 343 304–306 thalidomide 59 w thiolactomycin 454 whole-cell patch-clamp thymidylate synthase (TS)/dihydrofolate electrophysiology 318 reductase (DHFR) dual z inhibitors 177 Zucker diabetic fatty rat (ZDF) model tofacitinib 47 379 toxophores 147