THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets

1S6 Adiponectin receptorsS7 Blood coagulation componentsS8 Non‐enzymatic BRD containing proteinsS9 Carrier proteinsS9 CD moleculesS11 Methyllysine reader proteinsS11 Fatty acid‐binding proteinsS14 Notch receptorsS15 Regulators of G protein Signaling (RGS) proteinsS18 Sigma receptorsS19 Tubulins

2S6 Adiponectin receptors

3S7 Blood coagulation components

4S8 Non‐enzymatic BRD containing proteins

5S9 Carrier proteins

6S9 CD molecules

7S11 Methyllysine reader proteins

8S11 Fatty acid‐binding proteins

9S14 Notch receptors

10S15 Regulators of G protein Signaling (RGS) proteins

11S18 Sigma receptors

12S19 Tubulins

13S23 Orphan and other 7TM receptorsS24 Class A OrphansS26 Class C OrphansS33 Taste 1 receptorsS34 Taste 2 receptorsS35 Other 7TM proteinsS36 5‐Hydroxytryptamine receptorsS39 Acetylcholine receptors (muscarinic)S41 Adenosine receptorsS42 Adhesion Class GPCRsS45 AdrenoceptorsS48 Angiotensin receptorsS50 Apelin receptorS51 Bile acid receptorS51 Bombesin receptorsS53 Bradykinin receptorsS54 Calcitonin receptorsS56 Calcium‐sensing receptorS57 Cannabinoid receptorsS58 Chemerin receptorsS59 Chemokine receptorsS63 Cholecystokinin receptorsS64 Class Frizzled GPCRsS67 Complement peptide receptorsS68 Corticotropin‐releasing factor receptorsS69 Dopamine receptorsS71 Endothelin receptorsS72 G protein‐coupled estrogen receptorS73 Formylpeptide receptorsS74 Free fatty acid receptorsS76 GABAB receptorsS78 Galanin receptorsS79 Ghrelin receptorS80 Glucagon receptor familyS81 Glycoprotein hormone receptorsS82 Gonadotrophin‐releasing hormone receptorsS83 GPR18, GPR55 and GPR119S84 Histamine receptorsS86 Hydroxycarboxylic acid receptorsS87 Kisspeptin receptorS88 Leukotriene receptorsS89 Lysophospholipid (LPA) receptorsS90 Lysophospholipid (S1P) receptorsS92 Melanin‐concentrating hormone receptorsS93 Melanocortin receptorsS94 Melatonin receptorsS95 Metabotropic glutamate receptorsS97 Motilin receptorS98 Neuromedin U receptorsS99 Neuropeptide FF/neuropeptide AF receptorsS100 Neuropeptide S receptorS101 Neuropeptide W/neuropeptide B receptorsS102 Neuropeptide Y receptorsS103 Neurotensin receptorsS104 Opioid receptorsS106 Orexin receptorsS107 Oxoglutarate receptorS108 P2Y receptorsS110 Parathyroid hormone receptorsS111 Platelet‐activating factor receptorS112 Prokineticin receptorsS113 Prolactin‐releasing peptide receptorS114 Prostanoid receptorsS116 Proteinase‐activated receptorsS117 QRFP receptorS118 Relaxin family peptide receptorsS120 Somatostatin receptorsS121 Succinate receptorS122 Tachykinin receptorsS123 Thyrotropin‐releasing hormone receptorsS124 Trace amine receptorS125 Urotensin receptorS126 Vasopressin and oxytocin receptorsS127 VIP and PACAP receptors

14S23 Orphan and other 7TM receptors

15S24 Class A Orphans

16S26 Class C Orphans

17S33 Taste 1 receptors

18S34 Taste 2 receptors

19S35 Other 7TM proteins

20S36 5‐Hydroxytryptamine receptors

21S39 Acetylcholine receptors (muscarinic)

22S41 Adenosine receptors

23S42 Adhesion Class GPCRs

24S45 Adrenoceptors

25S48 Angiotensin receptors

26S50 Apelin receptor

27S51 Bile acid receptor

28S51 Bombesin receptors

29S53 Bradykinin receptors

30S54 Calcitonin receptors

31S56 Calcium‐sensing receptor

32S57 Cannabinoid receptors

33S58 Chemerin receptors

34S59 Chemokine receptors

35S63 Cholecystokinin receptors

36S64 Class Frizzled GPCRs

37S67 Complement peptide receptors

38S68 Corticotropin‐releasing factor receptors

39S69 Dopamine receptors

40S71 Endothelin receptors

41S72 G protein‐coupled estrogen receptor

42S73 Formylpeptide receptors

43S74 Free fatty acid receptors

44S76 GABAB receptors

45S78 Galanin receptors

46S79 Ghrelin receptor

47S80 Glucagon receptor family

48S81 Glycoprotein hormone receptors

49S82 Gonadotrophin‐releasing hormone receptors

50S83 GPR18, GPR55 and GPR119

51S84 Histamine receptors

52S86 Hydroxycarboxylic acid receptors

53S87 Kisspeptin receptor

54S88 Leukotriene receptors

55S89 Lysophospholipid (LPA) receptors

56S90 Lysophospholipid (S1P) receptors

57S92 Melanin‐concentrating hormone receptors

58S93 Melanocortin receptors

59S94 Melatonin receptors

60S95 Metabotropic glutamate receptors

61S97 Motilin receptor

62S98 Neuromedin U receptors

63S99 Neuropeptide FF/neuropeptide AF receptors

64S100 Neuropeptide S receptor

65S101 Neuropeptide W/neuropeptide B receptors

66S102 Neuropeptide Y receptors

67S103 Neurotensin receptors

68S104 Opioid receptors

69S106 Orexin receptors

70S107 Oxoglutarate receptor

71S108 P2Y receptors

72S110 Parathyroid hormone receptors

73S111 Platelet‐activating factor receptor

74S112 Prokineticin receptors

75S113 Prolactin‐releasing peptide receptor

76S114 Prostanoid receptors

77S116 Proteinase‐activated receptors

78S117 QRFP receptor

79S118 Relaxin family peptide receptors

80S120 Somatostatin receptors

81S121 Succinate receptor

82S122 Tachykinin receptors

83S123 Thyrotropin‐releasing hormone receptors

84S124 Trace amine receptor

85S125 Urotensin receptor

86S126 Vasopressin and oxytocin receptors

87S127 VIP and PACAP receptors

88S143 Ligand‐gated ion channelsS144 5‐HT3 receptorsS146 Acid‐sensing (proton‐gated) ion channels (ASICs)S148 Epithelial sodium channel (ENaC)S149 GABAA receptorsS155 Glycine receptorsS158 Ionotropic glutamate receptorsS164 IP3 receptorS165 Nicotinic acetylcholine receptorsS168 P2X receptorsS170 ZACS171 Voltage‐gated ion channelsS171 CatSper and Two‐Pore channelsS173 Cyclic nucleotide‐regulated channelsS175 Potassium channelsS175 Calcium‐ and sodium‐activated potassium channelsS178 Inwardly rectifying potassium channelsS182 Two P domain potassium channelsS185 Voltage‐gated potassium channelsS189 Ryanodine receptorsS190 Transient Receptor Potential channelsS204 Voltage‐gated calcium channelsS207 Voltage‐gated proton channelS208 Voltage‐gated sodium channelsS210 Other ion channelsS210 AquaporinsS212 Chloride channelsS213 ClC familyS215 CFTRS216 Calcium activated chloride channelS217 Maxi chloride channelS218 Volume regulated chloride channelsS219 Connexins and PannexinsS221 Piezo channelsS222 Sodium leak channel, non‐selective

89S143 Ligand‐gated ion channels

90S144 5‐HT3 receptors

91S146 Acid‐sensing (proton‐gated) ion channels (ASICs)

92S148 Epithelial sodium channel (ENaC)

93S149 GABAA receptors

94S155 Glycine receptors

95S158 Ionotropic glutamate receptors

96S164 IP3 receptor

97S165 Nicotinic acetylcholine receptors

98S168 P2X receptors

99S170 ZAC

100S171 Voltage‐gated ion channels

101S171 CatSper and Two‐Pore channels

102S173 Cyclic nucleotide‐regulated channels

103S175 Potassium channels

104S175 Calcium‐ and sodium‐activated potassium channels

105S178 Inwardly rectifying potassium channels

106S182 Two P domain potassium channels

107S185 Voltage‐gated potassium channels

108S189 Ryanodine receptors

109S190 Transient Receptor Potential channels

110S204 Voltage‐gated calcium channels

111S207 Voltage‐gated proton channel

112S208 Voltage‐gated sodium channels

113S210 Other ion channels

114S210 Aquaporins

115S212 Chloride channels

116S213 ClC family

117S215 CFTR

118S216 Calcium activated chloride channel

119S217 Maxi chloride channel

120S218 Volume regulated chloride channels

121S219 Connexins and Pannexins

122S221 Piezo channels

123S222 Sodium leak channel, non‐selective

124S230 1A. Thyroid hormone receptorsS231 1B. Retinoic acid receptorsS232 1C. Peroxisome proliferator‐activated receptorsS233 1D. Rev‐Erb receptorsS234 1F. Retinoic acid‐related orphansS234 1H. Liver X receptor‐like receptorsS235 1I. Vitamin D receptor‐like receptorsS236 2A. Hepatocyte nuclear factor‐4 receptorsS237 2B. Retinoid X receptorsS238 2C. Testicular receptorsS238 2E. Tailless‐like receptorsS239 2F. COUP‐TF‐like receptorsS239 3B. Estrogen‐related receptorsS240 4A. Nerve growth factor IB‐like receptorsS241 5A. Fushi tarazu F1‐like receptorsS241 6A. Germ cell nuclear factor receptorsS242 0B. DAX‐like receptorsS242 Steroid hormone receptorsS243 3A. Estrogen receptorsS244 3C. 3‐Ketosteroid receptors

125S230 1A. Thyroid hormone receptors

126S231 1B. Retinoic acid receptors

127S232 1C. Peroxisome proliferator‐activated receptors

128S233 1D. Rev‐Erb receptors

129S234 1F. Retinoic acid‐related orphans

130S234 1H. Liver X receptor‐like receptors

131S235 1I. Vitamin D receptor‐like receptors

132S236 2A. Hepatocyte nuclear factor‐4 receptors

133S237 2B. Retinoid X receptors

134S238 2C. Testicular receptors

135S238 2E. Tailless‐like receptors

136S239 2F. COUP‐TF‐like receptors

137S239 3B. Estrogen‐related receptors

138S240 4A. Nerve growth factor IB‐like receptors

139S241 5A. Fushi tarazu F1‐like receptors

140S241 6A. Germ cell nuclear factor receptors

141S242 0B. DAX‐like receptors

142S242 Steroid hormone receptors

143S243 3A. Estrogen receptors

144S244 3C. 3‐Ketosteroid receptors

145S248 Cytokine receptor familyS249 IL‐2 receptor familyS251 IL‐3 receptor familyS252 IL‐6 receptor familyS254 IL‐12 receptor familyS255 Prolactin receptor familyS256 Interferon receptor familyS257 IL‐10 receptor familyS258 Immunoglobulin‐like family of IL‐1 receptorsS259 IL‐17 receptor familyS259 GDNF receptor familyS260 IntegrinsS264 Pattern recognition receptorsS264 Toll‐like receptor familyS266 NOD‐like receptor familyS268 RIG‐I‐like receptor familyS269 Receptor Guanylyl Cyclase (RGC) familyS269 Transmembrane quanylyl cyclasesS270 Nitric oxide (NO)‐sensitive (soluble) guanylyl cyclaseS271 Receptor tyrosine kinases (RTKs)S272 Type I RTKs: ErbB (epidermal growth factor) receptor familyS273 Type II RTKs: Insulin receptor familyS274 Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor familyS275 Type IV RTKs: VEGF (vascular endothelial growth factor) receptor familyS275 Type V RTKs: FGF (broblast growth factor) receptor familyS276 Type VI RTKs: PTK7/CCK4S277 Type VII RTKs: Neurotrophin receptor/Trk familyS278 Type VIII RTKs: ROR familyS278 Type IX RTKs: MuSKS279 Type X RTKs: HGF (hepatocyte growth factor) receptor familyS279 Type XI RTKs: TAM (TYRO3‐, AXL‐ and MER‐TK) receptor familyS280 Type XII RTKs: TIE family of angiopoietin receptorsS280 Type XIII RTKs: Ephrin receptor familyS281 Type XIV RTKs: RETS282 Type XV RTKs: RYKS282 Type XVI RTKs: DDR (collagen receptor) familyS283 Type XVII RTKs: ROS receptorsS283 Type XVIII RTKs: LMR familyS284 Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor familyS284 Type XX RTKs: STYK1S286 Receptor serine/threonine kinase (RSTK) familyS286 Type I receptor serine/threonine kinasesS287 Type II receptor serine/threonine kinasesS287 Type III receptor serine/threonine kinasesS287 RSTK functional heteromersS289 Receptor tyrosine phosphatase (RTP) familyS291 Tumour necrosis factor (TNF) receptor family

146S248 Cytokine receptor family

147S249 IL‐2 receptor family

148S251 IL‐3 receptor family

149S252 IL‐6 receptor family

150S254 IL‐12 receptor family

151S255 Prolactin receptor family

152S256 Interferon receptor family

153S257 IL‐10 receptor family

154S258 Immunoglobulin‐like family of IL‐1 receptors

155S259 IL‐17 receptor family

156S259 GDNF receptor family

157S260 Integrins

158S264 Pattern recognition receptors

159S264 Toll‐like receptor family

160S266 NOD‐like receptor family

161S268 RIG‐I‐like receptor family

162S269 Receptor Guanylyl Cyclase (RGC) family

163S269 Transmembrane quanylyl cyclases

164S270 Nitric oxide (NO)‐sensitive (soluble) guanylyl cyclase

165S271 Receptor tyrosine kinases (RTKs)

166S272 Type I RTKs: ErbB (epidermal growth factor) receptor family

167S273 Type II RTKs: Insulin receptor family

168S274 Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

169S275 Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family

170S275 Type V RTKs: FGF (broblast growth factor) receptor family

171S276 Type VI RTKs: PTK7/CCK4

172S277 Type VII RTKs: Neurotrophin receptor/Trk family

173S278 Type VIII RTKs: ROR family

174S278 Type IX RTKs: MuSK

175S279 Type X RTKs: HGF (hepatocyte growth factor) receptor family

176S279 Type XI RTKs: TAM (TYRO3‐, AXL‐ and MER‐TK) receptor family

177S280 Type XII RTKs: TIE family of angiopoietin receptors

178S280 Type XIII RTKs: Ephrin receptor family

179S281 Type XIV RTKs: RET

180S282 Type XV RTKs: RYK

181S282 Type XVI RTKs: DDR (collagen receptor) family

182S283 Type XVII RTKs: ROS receptors

183S283 Type XVIII RTKs: LMR family

184S284 Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor family

185S284 Type XX RTKs: STYK1

186S286 Receptor serine/threonine kinase (RSTK) family

187S286 Type I receptor serine/threonine kinases

188S287 Type II receptor serine/threonine kinases

189S287 Type III receptor serine/threonine kinases

190S287 RSTK functional heteromers

191S289 Receptor tyrosine phosphatase (RTP) family

192S291 Tumour necrosis factor (TNF) receptor family

193S301 Acetylcholine turnoverS302 Adenosine turnoverS303 Amino acid hydroxylasesS304 L‐Arginine turnoverS304 2.1.1.‐ Protein arginine N‐methyltransferasesS305 ArginaseS305 Arginine:glycine amidinotransferaseS305 Dimethylarginine dimethylaminohydrolasesS306 Nitric oxide synthasesS307 Carbonic anhydrasesS308 Carboxylases and decarboxylasesS308 CarboxylasesS309 DecarboxylasesS311 Catecholamine turnoverS313 Ceramide turnoverS313 Serine palmitoyltransferaseS314 Ceramide synthaseS314 Sphingolipid Δ4‐desaturaseS315 Sphingomyelin synthaseS315 Sphingomyelin phosphodiesteraseS316 Neutral sphingomyelinase coupling factorsS316 Ceramide glucosyltransferaseS316 Acid ceramidaseS317 Neutral ceramidasesS317 Alkaline ceramidasesS318 Ceramide kinaseS319 Chromatin modifying enzymesS319 2.1.1.‐ Protein arginine N‐methyltransferasesS320 3.5.1.‐ Histone deacetylases (HDACs)S321 Cyclic nucleotide turnover/signallingS321 Adenylyl cyclases (ACs)S323 Exchange protein activated by cyclic AMP (EPACs)S323 Phosphodiesterases, 3’,5’‐cyclic nucleotide (PDEs)S327 Cytochrome P450S327 CYP2 familyS328 CYP2 familyS329 CYP3 familyS330 CYP4 familyS331 CYP5, CYP7 and CYP8 familiesS332 CYP11, CYP17, CYP19, CYP20 and CYP21 familiesS333 CYP24, CYP26 and CYP27 familiesS333 CYP39, CYP46 and CYP51 familiesS334 DNA topoisomerasesS335 Endocannabinoid turnoverS336 N‐Acylethanolamine turnoverS337 2‐Acylglycerol ester turnoverS338 Eicosanoid turnoverS338 CyclooxygenaseS339 Prostaglandin synthasesS341 LipoxygenasesS342 Leukotriene and lipoxin metabolismS343 GABA turnoverS344 Glycerophospholipid turnoverS345 Phosphoinositide‐specific phospholipase CS346 Phospholipase A2 S348 Phosphatidylcholine‐specific phospholipase DS349 Lipid phosphate phosphatasesS349 Phosphatidylinositol kinasesS350 1‐phosphatidylinositol 4‐kinase familyS351 Phosphatidylinositol‐4‐phosphate 3‐kinase familyS351 Phosphatidylinositol 3‐kinase familyS351 Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase familyS352 1‐phosphatidylinositol‐3‐phosphate 5‐kinase familyS353 Type I PIP kinases (1‐phosphatidylinositol‐4‐phosphate 5‐kinase family)S353 Type II PIP kinases (1‐phosphatidylinositol‐5‐phosphate 4‐kinase family)S356 Phosphatidylinositol phosphate kinasesS356 Haem oxygenaseS358 Hydrogen sulphide synthesisS358 HydrolasesS360 Inositol phosphate turnoverS360 Inositol 1,4,5‐trisphosphate 3‐kinasesS360 Inositol polyphosphate phosphatasesS361 Inositol monophosphataseS361 Kinases (EC 2.7.x.x)S362 Rho kinaseS362 Protein kinase C (PKC) familyS363 Alpha subfamilyS363 Delta subfamilyS364 Eta subfamilyS364 FRAP subfamilyS365 Cyclin‐dependent kinase (CDK) familyS365 CDK4 subfamilyS366 GSK subfamilyS367 Polo‐like kinase (PLK) familyS367 STE7 familyS368 Abl familyS368 Ack familyS369 Janus kinase (JakA) familyS369 Src familyS370 Tec familyS371 RAF familyS372 Lanosterol biosynthesis pathwayS374 Nucleoside synthesis and metabolismS376 Paraoxonase (PON) familyS377 Peptidases and proteinasesS377 A1: PepsinS377 A22: PresenilinS378 C14: CaspaseS378 M1: Aminopeptidase NS379 M2: Angiotensin‐converting (ACE and ACE2)S379 M10: Matrix metallopeptidaseS380 M12: Astacin/AdamalysinS380 M28: Aminopeptidase YS381 M19: Membrane dipeptidaseS381 S1: ChymotrypsinS382 T1: ProteasomeS382 S8: SubtilisinS383 S9: Prolyl oligopeptidaseS383 Poly ADP‐ribose polymerasesS384 Prolyl hydroxylasesS384 Sphingosine 1‐phosphate turnoverS385 Sphingosine kinaseS386 Sphingosine 1‐phosphate phosphataseS387 Sphingosine 1‐phosphate lyaseS387 Thyroid hormone turnoverS388 1.14.13.9 Kynurenine 3‐monooxygenaseS389 2.5.1.58 Protein farnesyltransferaseS390 3.5.1.‐ Histone deacetylases (HDACs)S391 3.5.3.15 Peptidyl arginine deiminases (PADI)S391 3.6.5.2 Small monomeric GTPasesS391 RAS subfamilyS392 RAB subfamily

194S301 Acetylcholine turnover

195S302 Adenosine turnover

196S303 Amino acid hydroxylases

197S304 L‐Arginine turnover

198S304 2.1.1.‐ Protein arginine N‐methyltransferases

199S305 Arginase

200S305 Arginine:glycine amidinotransferase

201S305 Dimethylarginine dimethylaminohydrolases

202S306 Nitric oxide synthases

203S307 Carbonic anhydrases

204S308 Carboxylases and decarboxylases

205S308 Carboxylases

206S309 Decarboxylases

207S311 Catecholamine turnover

208S313 Ceramide turnover

209S313 Serine palmitoyltransferase

210S314 Ceramide synthase

211S314 Sphingolipid Δ4‐desaturase

212S315 Sphingomyelin synthase

213S315 Sphingomyelin phosphodiesterase

214S316 Neutral sphingomyelinase coupling factors

215S316 Ceramide glucosyltransferase

216S316 Acid ceramidase

217S317 Neutral ceramidases

218S317 Alkaline ceramidases

219S318 Ceramide kinase

220S319 Chromatin modifying enzymes

221S319 2.1.1.‐ Protein arginine N‐methyltransferases

222S320 3.5.1.‐ Histone deacetylases (HDACs)

223S321 Cyclic nucleotide turnover/signalling

224S321 Adenylyl cyclases (ACs)

225S323 Exchange protein activated by cyclic AMP (EPACs)

226S323 Phosphodiesterases, 3’,5’‐cyclic nucleotide (PDEs)

227S327 Cytochrome P450

228S327 CYP2 family

229S328 CYP2 family

230S329 CYP3 family

231S330 CYP4 family

232S331 CYP5, CYP7 and CYP8 families

233S332 CYP11, CYP17, CYP19, CYP20 and CYP21 families

234S333 CYP24, CYP26 and CYP27 families

235S333 CYP39, CYP46 and CYP51 families

236S334 DNA topoisomerases

237S335 Endocannabinoid turnover

238S336 N‐Acylethanolamine turnover

239S337 2‐Acylglycerol ester turnover

240S338 Eicosanoid turnover

241S338 Cyclooxygenase

242S339 Prostaglandin synthases

243S341 Lipoxygenases

244S342 Leukotriene and lipoxin metabolism

245S343 GABA turnover

246S344 Glycerophospholipid turnover

247S345 Phosphoinositide‐specific phospholipase C

248S346 Phospholipase A2

249S348 Phosphatidylcholine‐specific phospholipase D

250S349 Lipid phosphate phosphatases

251S349 Phosphatidylinositol kinases

252S350 1‐phosphatidylinositol 4‐kinase family

253S351 Phosphatidylinositol‐4‐phosphate 3‐kinase family

254S351 Phosphatidylinositol 3‐kinase family

255S351 Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase family

256S352 1‐phosphatidylinositol‐3‐phosphate 5‐kinase family

257S353 Type I PIP kinases (1‐phosphatidylinositol‐4‐phosphate 5‐kinase family)

258S353 Type II PIP kinases (1‐phosphatidylinositol‐5‐phosphate 4‐kinase family)

259S356 Phosphatidylinositol phosphate kinases

260S356 Haem oxygenase

261S358 Hydrogen sulphide synthesis

262S358 Hydrolases

263S360 Inositol phosphate turnover

264S360 Inositol 1,4,5‐trisphosphate 3‐kinases

265S360 Inositol polyphosphate phosphatases

266S361 Inositol monophosphatase

267S361 Kinases (EC 2.7.x.x)

268S362 Rho kinase

269S362 Protein kinase C (PKC) family

270S363 Alpha subfamily

271S363 Delta subfamily

272S364 Eta subfamily

273S364 FRAP subfamily

274S365 Cyclin‐dependent kinase (CDK) family

275S365 CDK4 subfamily

276S366 GSK subfamily

277S367 Polo‐like kinase (PLK) family

278S367 STE7 family

279S368 Abl family

280S368 Ack family

281S369 Janus kinase (JakA) family

282S369 Src family

283S370 Tec family

284S371 RAF family

285S372 Lanosterol biosynthesis pathway

286S374 Nucleoside synthesis and metabolism

287S376 Paraoxonase (PON) family

288S377 Peptidases and proteinases

289S377 A1: Pepsin

290S377 A22: Presenilin

291S378 C14: Caspase

292S378 M1: Aminopeptidase N

293S379 M2: Angiotensin‐converting (ACE and ACE2)

294S379 M10: Matrix metallopeptidase

295S380 M12: Astacin/Adamalysin

296S380 M28: Aminopeptidase Y

297S381 M19: Membrane dipeptidase

298S381 S1: Chymotrypsin

299S382 T1: Proteasome

300S382 S8: Subtilisin

301S383 S9: Prolyl oligopeptidase

302S383 Poly ADP‐ribose polymerases

303S384 Prolyl hydroxylases

304S384 Sphingosine 1‐phosphate turnover

305S385 Sphingosine kinase

306S386 Sphingosine 1‐phosphate phosphatase

307S387 Sphingosine 1‐phosphate lyase

308S387 Thyroid hormone turnover

309S388 1.14.13.9 Kynurenine 3‐monooxygenase

310S389 2.5.1.58 Protein farnesyltransferase

311S390 3.5.1.‐ Histone deacetylases (HDACs)

312S391 3.5.3.15 Peptidyl arginine deiminases (PADI)

313S391 3.6.5.2 Small monomeric GTPases

314S391 RAS subfamily

315S392 RAB subfamily

316S399 ATP‐binding cassette transporter familyS399 ABCA subfamilyS401 ABCB subfamilyS403 ABCC subfamilyS404 ABCD subfamily of peroxisomal ABC transportersS405 ABCG subfamilyS406 F‐type and V‐type ATPasesS406 F‐type ATPaseS407 V‐type ATPaseS407 P‐type ATPasesS407 Na+/K+‐ATPasesS408 Ca2+‐ATPasesS408 H+/K+‐ATPasesS408 Cu+‐ATPasesS409 Phospholipid‐transporting ATPasesS409 SLC superfamily of solute carriersS410 SLC1 family of amino acid transportersS410 Glutamate transporter subfamilyS412 Alanine/serine/cysteine transporter subfamilyS413 SLC2 family of hexose and sugar alcohol transportersS413 Class I transportersS414 Class II transportersS415 Proton‐coupled inositol transporterS415 SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)S415 SLC3 familyS416 SLC7 familyS417 SLC4 family of bicarbonate transportersS417 Anion exchangersS418 Sodium‐dependent HCO3 − transportersS418 SLC5 family of sodium‐dependent glucose transportersS419 Hexose transporter familyS420 Choline transporterS421 Sodium iodide symporter, sodium‐dependent multivitamin transporter and sodium‐coupled monocarboxylate transportersS422 Sodium myo‐inositol cotransporter transportersS423 SLC6 neurotransmitter transporter familyS423 Monoamine transporter subfamilyS424 GABA transporter subfamilyS425 Glycine transporter subfamilyS427 Neutral amino acid transporter subfamilyS428 SLC8 family of sodium/calcium exchangersS429 SLC9 family of sodium/hydrogen exchangersS429 SLC10 family of sodium‐bile acid co‐transportersS431 SLC11 family of proton‐coupled metal ion transportersS431 SLC12 family of cation‐coupled chloride transportersS433 SLC13 family of sodium‐dependent sulphate/carboxylate transportersS434 SLC14 family of facilitative urea transportersS435 SLC15 family of peptide transportersS437 SLC16 family of monocarboxylate transportersS438 SLC17 phosphate and organic anion transporter familyS438 Type I sodium‐phosphate co‐transportersS439 Sialic acid transporterS439 Vesicular glutamate transporters (VGLUTs)S440 Vesicular nucleotide transporterS440 SLC18 family of vesicular amine transportersS442 SLC19 family of vitamin transportersS443 SLC20 family of sodium‐dependent phosphate transportersS443 SLC22 family of organic cation and anion transportersS444 Organic cation transporters (OCT)S445 Organic zwitterions/cation transporters (OCTN)S446 Organic anion transporters (OATs)S446 Urate transporterS447 Atypical SLC22B subfamilyS448 SLC23 family of ascorbic acid transportersS449 SLC24 family of sodium/potassium/calcium exchangersS450 SLC25 family of mitochondrial transportersS450 Mitochondrial di‐ and tri‐carboxylic acid transporter subfamilyS451 Mitochondrial amino acid transporter subfamilyS452 Mitochondrial phosphate transportersS452 Mitochondrial nucleotide transporter subfamilyS453 Mitochondrial uncoupling proteinsS454 Miscellaneous SLC25 mitochondrial transportersS454 SLC26 family of anion exchangersS454 Selective sulphate transportersS455 Chloride/bicarbonate exchangersS455 Anion channelsS456 Other SLC26 anion exchangersS457 SLC27 family of fatty acid transportersS458 SLC28 and SLC29 families of nucleoside transportersS458 SLC28 familyS459 SLC29 familyS461 SLC30 zinc transporter familyS461 SLC31 family of copper transportersS462 SLC32 vesicular inhibitory amino acid transporterS463 SLC33 acetylCoA transporterS464 SLC34 family of sodium phosphate co‐transportersS465 SLC35 family of nucleotide sugar transportersS466 SLC36 family of proton‐coupled amino acid transportersS468 SLC37 family of phosphosugar/phosphate exchangersS468 SLC38 family of sodium‐dependent neutral amino acid transportersS469 System A‐like transportersS469 System N‐like transportersS470 Orphan SLC38 transportersS470 SLC39 family of metal ion transportersS471 SLC40 iron transporterS472 SLC41 family of divalent cation transportersS473 SLC42 family of Rhesus glycoprotein ammoniumtransportersS473 SLC43 family of large neutral amino acid transportersS474 SLC44 choline transporter‐like familyS475 SLC45 family of putative sugar transportersS475 SLC46 family of folate transportersS477 SLC47 family of multidrug and toxin extrusion transportersS477 SLC48 heme transporterS478 SLC49 family of FLVCR‐related heme transportersS479 SLC50 sugar transporterS479 SLC51 family of steroid‐derived molecule transportersS480 SLC52 family of riboflavin transportersS481 SLC53 Phosphate carriersS481 SLC54 Mitochondrial pyruvate carriersS482 SLC55 Mitochondrial cation/proton exchangersS482 SLC56 SideroflexinsS483 SLC57 NiPA‐like magnesium transporter familyS483 SLC58 MagT‐like magnesium transporter familyS484 SLC59 Sodium‐dependent lysophosphatidylcholine symporter familyS484 SLC60 Glucose transportersS485 SLC61 Molybdate transporter familyS485 SLC62 Pyrophosphate transportersS486 SLC63 Sphingosine phosphate transportersS486 SLC64 Golgi Ca2+/H+ exchangersS487 SLC65 NPC‐type cholesterol transportersS488 SLCO family of organic anion transporting polypeptides

317S399 ATP‐binding cassette transporter family

318S399 ABCA subfamily

319S401 ABCB subfamily

320S403 ABCC subfamily

321S404 ABCD subfamily of peroxisomal ABC transporters

322S405 ABCG subfamily

323S406 F‐type and V‐type ATPases

324S406 F‐type ATPase

325S407 V‐type ATPase

326S407 P‐type ATPases

327S407 Na+/K+‐ATPases

328S408 Ca2+‐ATPases

329S408 H+/K+‐ATPases

330S408 Cu+‐ATPases

331S409 Phospholipid‐transporting ATPases

332S409 SLC superfamily of solute carriers

333S410 SLC1 family of amino acid transporters

334S410 Glutamate transporter subfamily

335S412 Alanine/serine/cysteine transporter subfamily

336S413 SLC2 family of hexose and sugar alcohol transporters

337S413 Class I transporters

338S414 Class II transporters

339S415 Proton‐coupled inositol transporter

340S415 SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

341S415 SLC3 family

342S416 SLC7 family

343S417 SLC4 family of bicarbonate transporters

344S417 Anion exchangers

345S418 Sodium‐dependent HCO3 − transporters

346S418 SLC5 family of sodium‐dependent glucose transporters

347S419 Hexose transporter family

348S420 Choline transporter

349S421 Sodium iodide symporter, sodium‐dependent multivitamin transporter and sodium‐coupled monocarboxylate transporters

350S422 Sodium myo‐inositol cotransporter transporters

351S423 SLC6 neurotransmitter transporter family

352S423 Monoamine transporter subfamily

353S424 GABA transporter subfamily

354S425 Glycine transporter subfamily

355S427 Neutral amino acid transporter subfamily

356S428 SLC8 family of sodium/calcium exchangers

357S429 SLC9 family of sodium/hydrogen exchangers

358S429 SLC10 family of sodium‐bile acid co‐transporters

359S431 SLC11 family of proton‐coupled metal ion transporters

360S431 SLC12 family of cation‐coupled chloride transporters

361S433 SLC13 family of sodium‐dependent sulphate/carboxylate transporters

362S434 SLC14 family of facilitative urea transporters

363S435 SLC15 family of peptide transporters

364S437 SLC16 family of monocarboxylate transporters

365S438 SLC17 phosphate and organic anion transporter family

366S438 Type I sodium‐phosphate co‐transporters

367S439 Sialic acid transporter

368S439 Vesicular glutamate transporters (VGLUTs)

369S440 Vesicular nucleotide transporter

370S440 SLC18 family of vesicular amine transporters

371S442 SLC19 family of vitamin transporters

372S443 SLC20 family of sodium‐dependent phosphate transporters

373S443 SLC22 family of organic cation and anion transporters

374S444 Organic cation transporters (OCT)

375S445 Organic zwitterions/cation transporters (OCTN)

376S446 Organic anion transporters (OATs)

377S446 Urate transporter

378S447 Atypical SLC22B subfamily

379S448 SLC23 family of ascorbic acid transporters

380S449 SLC24 family of sodium/potassium/calcium exchangers

381S450 SLC25 family of mitochondrial transporters

382S450 Mitochondrial di‐ and tri‐carboxylic acid transporter subfamily

383S451 Mitochondrial amino acid transporter subfamily

384S452 Mitochondrial phosphate transporters

385S452 Mitochondrial nucleotide transporter subfamily

386S453 Mitochondrial uncoupling proteins

387S454 Miscellaneous SLC25 mitochondrial transporters

388S454 SLC26 family of anion exchangers

389S454 Selective sulphate transporters

390S455 Chloride/bicarbonate exchangers

391S455 Anion channels

392S456 Other SLC26 anion exchangers

393S457 SLC27 family of fatty acid transporters

394S458 SLC28 and SLC29 families of nucleoside transporters

395S458 SLC28 family

396S459 SLC29 family

397S461 SLC30 zinc transporter family

398S461 SLC31 family of copper transporters

399S462 SLC32 vesicular inhibitory amino acid transporter

400S463 SLC33 acetylCoA transporter

401S464 SLC34 family of sodium phosphate co‐transporters

402S465 SLC35 family of nucleotide sugar transporters

403S466 SLC36 family of proton‐coupled amino acid transporters

404S468 SLC37 family of phosphosugar/phosphate exchangers

405S468 SLC38 family of sodium‐dependent neutral amino acid transporters

406S469 System A‐like transporters

407S469 System N‐like transporters

408S470 Orphan SLC38 transporters

409S470 SLC39 family of metal ion transporters

410S471 SLC40 iron transporter

411S472 SLC41 family of divalent cation transporters

412S473 SLC42 family of Rhesus glycoprotein ammoniumtransporters

413S473 SLC43 family of large neutral amino acid transporters

414S474 SLC44 choline transporter‐like family

415S475 SLC45 family of putative sugar transporters

416S475 SLC46 family of folate transporters

417S477 SLC47 family of multidrug and toxin extrusion transporters

418S477 SLC48 heme transporter

419S478 SLC49 family of FLVCR‐related heme transporters

420S479 SLC50 sugar transporter

421S479 SLC51 family of steroid‐derived molecule transporters

422S480 SLC52 family of riboflavin transporters

423S481 SLC53 Phosphate carriers

424S481 SLC54 Mitochondrial pyruvate carriers

425S482 SLC55 Mitochondrial cation/proton exchangers

426S482 SLC56 Sideroflexins

427S483 SLC57 NiPA‐like magnesium transporter family

428S483 SLC58 MagT‐like magnesium transporter family

429S484 SLC59 Sodium‐dependent lysophosphatidylcholine symporter family

430S484 SLC60 Glucose transporters

431S485 SLC61 Molybdate transporter family

432S485 SLC62 Pyrophosphate transporters

433S486 SLC63 Sphingosine phosphate transporters

434S486 SLC64 Golgi Ca2+/H+ exchangers

435S487 SLC65 NPC‐type cholesterol transporters

436S488 SLCO family of organic anion transporting polypeptides

437In order to allow clarity and consistency in pharmacology, there is a need for a comprehensive organisation and presentation of the targets of drugs. This is the philosophy of the IUPHAR/BPS Guide to PHARMACOLOGY presented on the online free access database (https://www.guidetopharmacology.org/). This database is supported by the British Pharmacological Society (BPS), the International Union of Basic and Clinical Pharmacology (IUPHAR), the University of Edinburgh and previously the Wellcome Trust. Data included in the Guide to PHARMACOLOGY are derived in large part from interactions with the subcommittees of the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR). A major influence on the development of the database was Tony Harmar (1951‐2014), who worked with a passion to establish the curators as a team of highly informed and informative individuals, with a focus on high‐quality data input, ensuring a suitably validated dataset. The Editors of the Concise Guide have compiled the individual records, in concert with the team of Curators, drawing on the expert knowledge of these latter subcommittees. The tables allow an indication of the status of the nomenclature for the group of targets listed, usually previously published in Pharmacological Reviews. In the absence of an established subcommittee, advice from several prominent, independent experts has generally been obtained to produce an authoritative consensus on nomenclature, which attempts to fit in within the general guidelines from NC‐IUPHAR. This current edition, the Concise Guide to PHARMACOLOGY 2019/20, is the latest snapshot of the database in print form, following on from the Concise Guide to PHARMACOLOGY 2017/18. It contains data drawn from the online database as a rapid overview of the major pharmacological targets. Thus, there are many fewer targets presented in the Concise Guide compared to the online database. The priority for inclusion in the Concise Guide is the presence of quantitative pharmacological data for human proteins. This means that often orphan family members are not presented in the Concise Guide, although structural information is available on the online database. The organisation of the data is tabular (where appropriate) with a standardised format, where possible on a single page, intended to aid understanding of, and comparison within, a particular target group. The Concise Guide is intended as an initial resource, with links to additional reviews and resources for greater depth and information. Pharmacological and structural data focus primarily on human gene products, wherever possible, with links to HGNC gene nomenclature and UniProt IDs. In a few cases, where data from human proteins are limited, data from other species are indicated. Pharmacological tools listed are prioritised on the basis of selectivity and availability. That is, agents (agonists, antagonists, inhibitors, activators, etc.) are included where they are both available (by donation or from commercial sources, now or in the near future) AND the most selective. The Concise Guide is divided into seven sections, which comprise pharmacological targets of similar structure/function. These are G protein‐coupled receptors, ion channels (combining previous records of ligand‐gated, voltage‐gated and other ion channels), catalytic receptors, nuclear hormone receptors, enzymes, transporters and other protein targets. We hope that the Concise Guide will provide for researchers, teachers and students a state‐of‐the art source of accurate, curated information on the background to their work that they will use in the Introductions to their Research Papers or Reviews, or in supporting their teaching and studies. We recommend that any citations to information in the Concise Guide are presented in the following format: Alexander SPH et al. (2019). The Concise Guide to PHARMACOLOGY 2019/20: Introduction and Other Protein Targets. Br J Pharmacol 176: S1–S20. In this overview are listed protein targets of pharmacological interest, which are not G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, transporters or enzymes.

438We are extremely grateful to the British Pharmacological Society and the International Union of Basic and Clinical Pharmacology, for financial support of the website and for advice from the NC‐IUPHAR subcommittees. We thank the University of Edinburgh, who host the http://www.guidetopharmacology.org website. Previously, the International Union of Basic and Clinical Pharmacology and the Wellcome Trust (099156/Z/12/Z]) also supported the initiation and expansion of the database. We are also tremendously grateful to the long list of collaborators from NC‐IUPHAR subcommittees and beyond, who have assisted in the construction of the Concise Guide to PHARMACOLOGY 2019/20 and the online database http://www.guidetopharmacology.org.

439The authors state that there are no conflicts of interest to disclose.

440– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1021

441S6 Adiponectin receptors

442– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=982

443– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=970

444– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=983

445– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=971

446– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=910

447S7 Blood coagulation components

448– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=866

449S8 Non‐enzymatic BRD containing proteins

450– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=966

451S8 Carrier proteins

452S9 CD molecules

453– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=997

454– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=998

455– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=986

456– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=901

457S11 Methyllysine reader proteins

458– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=916

459– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=930

460– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=915

461S11 Fatty acid-binding proteins

462– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=946

463– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=935

464– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=784

465– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=954

466– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=949

467– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=985

468– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=987

469– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=984

470– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=868

471– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=889

472– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=876

473– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=888

474– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=934

475– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=924

476– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=919

477– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=921

478– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=991

479– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=941

480– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=942

481– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=945

482– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=929

483S14 Notch receptors

484– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1001

485– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=906

486– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=907

487S15 Regulators of G protein Signaling (RGS) proteins

488S15 RZ family

489S15 R4 family

490S16 R7 family

491S17 R12 family

492– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=932

493– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=905

494– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=875

495– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1000

496S18 Sigma receptors

497– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=989

498– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=972

499– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1019

500– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=973

501– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=974

502– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=990

503– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=995

504– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=996

505S19 Tubulins

506– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=904

507– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=903

508Adiponectin receptors (provisional nomenclature, http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00500000270960) respond to the 30 kDa complement‐related protein hormone adiponectin (also known as https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633: adipocyte, C1q and collagen domain‐containing protein; ACRP30, adipose most abundant gene transcript 1; apM‐1; gelatin‐binding protein: http://www.uniprot.org/uniprot/Q15848) originally cloned from adipocytes [http://www.ncbi.nlm.nih.gov/pubmed/8619847?dopt=AbstractPlus]. Although sequence data suggest 7TM domains, immunological evidence indicates that, contrary to typical 7TM topology, the carboxyl terminus is extracellular, while the amino terminus is intracellular [http://www.ncbi.nlm.nih.gov/pubmed/12802337?dopt=AbstractPlus]. Signalling through these receptors appears to avoid G proteins; modelling based on the crystal structures of the adiponectin receptors suggested ceramidase acivity, which would make these the first in a new family of catalytic receptors [http://www.ncbi.nlm.nih.gov/pubmed/25855295?dopt=AbstractPlus].

509T‐Cadherin (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1753, http://www.uniprot.org/uniprot/P55290) has also been suggested to be a receptor for (hexameric) adiponectin [http://www.ncbi.nlm.nih.gov/pubmed/15210937?dopt=AbstractPlus].

510Fisman EZ et al. (2014) Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol 13: 103 [https://www.ncbi.nlm.nih.gov/pubmed/24957699?dopt=AbstractPlus]

511Okada‐Iwabu M et al. (2018) Structure and function analysis of adiponectin receptors toward development of novel antidiabetic agents promoting healthy longevity. Endocr J 65: 971‐977 [https://www.ncbi.nlm.nih.gov/pubmed/30282888]

512Ruan H et al. (2016) Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol 8: 101‐9 [https://www.ncbi.nlm.nih.gov/pubmed/26993044?dopt=AbstractPlus]

513Wang Y et al. (2017) Cardiovascular Adiponectin Resistance: The Critical Role of Adiponectin Receptor Modification. Trends Endocrinol. Metab. 28: 519‐530 [https://www.ncbi.nlm.nih.gov/pubmed/28473178?dopt=AbstractPlus]

514Zhao L et al. (2014) Adiponectin and insulin cross talk: the microvascular connection. Trends Cardiovasc. Med. 24: 319‐24 [https://www.ncbi.nlm.nih.gov/pubmed/25220977?dopt=AbstractPlus]

515Coagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel‐like clot local to the site of injury. The process involves the activation, adhesion (see http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=760), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors, typically through proteolysis (see http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=759&familyType=ENZYME). Listed here are the components of the coagulation cascade targetted by agents in current clinical usage.

516Astermark J. (2015) FVIII inhibitors: pathogenesis and avoidance. Blood 125: 2045‐51 [https://www.ncbi.nlm.nih.gov/pubmed/25712994?dopt=AbstractPlus]

517Girolami A et al. (2017) New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice. J. Thromb. Thrombolysis 44: 71‐75 [https://www.ncbi.nlm.nih.gov/pubmed/28251495?dopt=AbstractPlus]

518Rana K et al. (2016) Blood flow and mass transfer regulation of coagulation. Blood Rev. 30: 357‐68 [https://www.ncbi.nlm.nih.gov/pubmed/27133256?dopt=AbstractPlus]

519Bromodomains bind proteins with acetylated lysine residues, such as histones, to regulate gene transcription. Listed herein are examples of bromodomain‐containing proteins for which sufficient pharmacology exists.

520Fujisawa T et al. (2017) Functions of bromodomain‐containing proteins and their roles in homeostasis and cancer. Nat. Rev. Mol. Cell Biol. 18: 246‐262 [https://www.ncbi.nlm.nih.gov/pubmed/28053347?dopt=AbstractPlus]

521Myrianthopoulos V & Mikros E. (2019) From bench to bedside, via desktop. Recent advances in the application of cutting‐edge in silico tools in the research of drugs targeting bromodomain modules. Biochem Pharmacol 159: 40‐51 [https://www.ncbi.nlm.nih.gov/pubmed/30414936]

522Nicholas DA et al. (2017) BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer. Cell. Mol. Life Sci. 74: 231‐243 [https://www.ncbi.nlm.nih.gov/pubmed/27491296?dopt=AbstractPlus]

523Ramadoss M & Mahadevan V. (2018) Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors. Drug Discov Today 23: 76‐89 [https://www.ncbi.nlm.nih.gov/pubmed/28943305]

524Yang CY et al. (2019) Small‐molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins ‐ A review. Drug Discov Today Technol 31: 43‐51 [https://www.ncbi.nlm.nih.gov/pubmed/31200858]

525Transthyretin (TTR) is a homo‐tetrameric protein which transports thyroxine in the plasma and cerebrospinal fluid and retinol (vitamin A) in the plasma. Many disease causing mutations in the protein have been reported, many of which cause complex dissociation and protein mis‐assembly and deposition of toxic aggregates amyloid fibril formation [http://www.ncbi.nlm.nih.gov/pubmed/23716704?dopt=AbstractPlus]. These amyloidogenic mutants are linked to the development of pathological amyloidoses, including familial amyloid polyneuropathy (FAP) [http://www.ncbi.nlm.nih.gov/pubmed/12978172?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/8894411?dopt=AbstractPlus], familial amyloid cardiomyopathy (FAC) [http://www.ncbi.nlm.nih.gov/pubmed/9017939?dopt=AbstractPlus], amyloidotic vitreous opacities, carpal tunnel syndrome [http://www.ncbi.nlm.nih.gov/pubmed/10403814?dopt=AbstractPlus] and others. In old age, non‐mutated TTR can also form pathological amyloid fibrils [http://www.ncbi.nlm.nih.gov/pubmed/7016817?dopt=AbstractPlus]. Pharmacological intervention to reduce or prevent TTR dissociation is being pursued as a theapeutic strategy. To date one small molecule kinetic stabilising molecule (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8378) has been approved for FAP, and is being evaluated in clinical trials for other TTR amyloidoses.

526Adams D et al. (2019) Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol 15: 387‐404 [https://www.ncbi.nlm.nih.gov/pubmed/31209302]

527Dellière S et al. (2017) Is transthyretin a good marker of nutritional status? Clin Nutr 36: 364‐370 [https://www.ncbi.nlm.nih.gov/pubmed/27381508?dopt=AbstractPlus]

528Galant NJ et al. (2017) Transthyretin amyloidosis: an under‐recognized neuropathy and cardiomyopathy. Clin. Sci. 131: 395‐409 [https://www.ncbi.nlm.nih.gov/pubmed/28213611?dopt=AbstractPlus]

529Yokoyama T & Mizuguchi M. (2018) Inhibition of the Amyloidogenesis of Transthyretin by Natural Products and Synthetic Compounds. Biol Pharm Bull 41: 979‐984 [https://www.ncbi.nlm.nih.gov/pubmed/29962408]

530Ruberg FL et al. (2019) Transthyretin Amyloid Cardiomyopathy: JACC State‐of‐the‐Art Review. J Am Coll Cardiol 73: 2872‐2891 [https://www.ncbi.nlm.nih.gov/pubmed/31171094]

531Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell‐surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes (for example, see http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1232) or receptors (for example, see http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2441). Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.

532The endogenous ligands for human PD‐1 are programmed cell death 1 ligand 1 (PD‐L1 aka http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7693 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17635, http://www.uniprot.org/uniprot/Q9NZQ7)) and programmed cell death 1 ligand 2 (PD‐L2; https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18731). These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD‐1 by cancer cells induces immune tolerance and evasion of immune system attack. Anti‐PD‐1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re‐establishing immune vigilance. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7499 was the first anti‐PD‐1 antibody to be approved by the US FDA.

533Gabius HJ et al. (2015) The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem. Sci. 40: 360‐76 [https://www.ncbi.nlm.nih.gov/pubmed/25981696?dopt=AbstractPlus]

534Vosoughi T et al. (2019) CD markers variations in chronic lymphocytic leukemia: New insights into prognosis. J Cell Physiol. 234: 19420‐39 [https://www.ncbi.nlm.nih.gov/pubmed/31049958]

535Methyllysine reader proteins bind to methylated proteins, such as histones, allowing regulation of gene expression.

536Daskalaki MG et al. (2018) Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J Cell Physiol. 233: 6495‐9507 [https://www.ncbi.nlm.nih.gov/pubmed/29574768]

537Furuya K et al. (2019) Epigenetic interplays between DNA demethylation and histone methylation for protecting oncogenesis. J Biochem. 165: 297‐299 [https://www.ncbi.nlm.nih.gov/pubmed/30605533]

538Levy D. (2019) Lysine methylation signaling of non‐histone proteins in the nucleus. Cell Mol Life Sci 76: 2873‐83 [https://www.ncbi.nlm.nih.gov/pubmed/31123776]

539Li J et al. (2019) Understanding histone H3 lysine 36 methylation and its deregulation in disease. Cell Mol Life Sci in press [https://www.ncbi.nlm.nih.gov/pubmed/31147750]

540Shafabakhsh R et al. (2019) Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy. J Cell Physiol. 234: 7839‐7846 [https://www.ncbi.nlm.nih.gov/pubmed/30515789]

541Fatty acid‐binding proteins are low molecular weight (100‐130 aa) chaperones for long chain fatty acids, fatty acyl CoA esters, eicosanoids, retinols, retinoic acids and related metabolites and are usually regarded as being responsible for allowing the otherwise hydrophobic ligands to be mobile in aqueous media. These binding proteins may perform functions extracellularly (e.g. in plasma) or transport these agents; to the nucleus to interact with nuclear receptors (principally PPARs and retinoic acid receptors http://www.ncbi.nlm.nih.gov/pubmed/17882463?dopt=AbstractPlus]) or for interaction with metabolic enzymes. Although sequence homology is limited, crystallographic studies suggest conserved 3D structures across the group of binding proteins.

542Although not tested at all FABPs, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6735 exhibits high affinity for FABP4 (pIC50 8.8) compared to FABP3 or FABP5 (pIC50 <6.6) [http://www.ncbi.nlm.nih.gov/pubmed/17554340?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/17502136?dopt=AbstractPlus]. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6736 is reported to interfere with FABP4 action [http://www.ncbi.nlm.nih.gov/pubmed/19754198?dopt=AbstractPlus]. Ibuprofen displays some selectivity for FABP4 (pIC50 5.5) relative to FABP3 (pIC50 3.5) and FABP5 (pIC50 3.8) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Fenofibric acid displays some selectivity for FABP5 (pIC50 5.5) relative to FABP3 (pIC50 4.5) and FABP4 (pIC50 4.6) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Multiple pseudogenes for the FABPs have been identified in the human genome.

543Gajda AM et al. (2015) Enterocyte fatty acid‐binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot. Essent. Fatty Acids 93: 9‐16 [https://www.ncbi.nlm.nih.gov/pubmed/25458898?dopt=AbstractPlus]

544Glatz JF. (2015) Lipids and lipid binding proteins: a perfect match. Prostaglandins Leukot Essent Fatty Acids 93: 45‐9 [https://www.ncbi.nlm.nih.gov/pubmed/25154384?dopt=AbstractPlus]

545Hotamisligil GS et al. (2015) Metabolic functions of FABPs–mechanisms and therapeutic implications. Nat Rev Endocrinol 11: 592‐605 [https://www.ncbi.nlm.nih.gov/pubmed/26260145?dopt=AbstractPlus]

546Matsumata M et al. (2016) Fatty acid binding proteins and the nervous system: Their impact on mental conditions. Neurosci. Res. 102: 47‐55 [https://www.ncbi.nlm.nih.gov/pubmed/25205626?dopt=AbstractPlus]

547Osumi T et al. (2016) Heart lipid droplets and lipid droplet‐binding proteins: Biochemistry, physiology, and pathology. Exp. Cell Res. 340: 198‐204 [https://www.ncbi.nlm.nih.gov/pubmed/26524506?dopt=AbstractPlus]

548The canonical Notch signalling pathway has four type I transmembrane Notch receptors (Notch1‐4) and five ligands (DLL1, 2 and 3, and Jagged 1‐2). Each member of this highly conserved receptor family plays a unique role in cell‐fate determination during embryogenesis, differentiation, tissue patterning, proliferation and cell death [http://www.ncbi.nlm.nih.gov/pubmed/20971825?dopt=AbstractPlus]. As the Notch ligands are also membrane bound, cells have to be in close proximity for receptorligand interactions to occur. Cleavage of the intracellular domain (ICD) of activated Notch receptors by γ‐secretase is required for downstream signalling and Notch‐induced transcriptional modulation [http://www.ncbi.nlm.nih.gov/pubmed/10206645?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/16530044?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9620803?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/16530045?dopt=AbstractPlus]. This is why γ‐secretase inhibitors can be used to downregulate Notch signalling and explains their anticancer action. One such small molecule is http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7338 [http://www.ncbi.nlm.nih.gov/pubmed/19773430?dopt=AbstractPlus], although development of this compound has been terminated following an unsuccessful Phase II single agent clinical trial in metastatic colorectal cancer [http://www.ncbi.nlm.nih.gov/pubmed/22445247?dopt=AbstractPlus].

549Aberrant Notch signalling is implicated in a number of human cancers [http://www.ncbi.nlm.nih.gov/pubmed/17344417?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/24651013?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/18079963?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/17173050?dopt=AbstractPlus], with http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8451 and http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8453 identified as antibody inhibitors of ligand:receptor binding [http://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus].

550Arumugam TV et al. (2018) Notch signaling and neuronal death in stroke. Prog. Neurobiol. 165‐167: 103‐116 [https://www.ncbi.nlm.nih.gov/pubmed/29574014?dopt=AbstractPlus]

551Borggrefe T et al. (2016) The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways. Biochim. Biophys. Acta 1863: 303‐13 [https://www.ncbi.nlm.nih.gov/pubmed/26592459?dopt=AbstractPlus]

552Palmer WH et al. (2015) Ligand‐Independent Mechanisms of Notch Activity. Trends Cell Biol. 25: 697‐707 [https://www.ncbi.nlm.nih.gov/pubmed/26437585?dopt=AbstractPlus]

553Previs RA et al. (2015) Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin. Cancer Res. 21: 955‐61 [https://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus]

554Takebe N et al. (2015) Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12: 445‐64 [https://www.ncbi.nlm.nih.gov/pubmed/25850553?dopt=AbstractPlus]

555Regulators of G protein signalling (RGS) proteins display a common RGS domain that interacts with the GTP‐bound Gα subunits of heterotrimeric G proteins, enhancing GTP hydrolysis by stabilising the transition state [http://www.ncbi.nlm.nih.gov/pubmed/8756726?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9108480?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9417641?dopt=AbstractPlus], leading to a termination of GPCR signalling. Interactions through protein: protein interactions of many RGS proteins have been identified for targets other than heteromeric G proteins. Sequence analysis of the 20 RGS proteins suggests four families of RGS: RZ, R4, R7 and R12 families. Many of these proteins have been identified to have effects other than through targetting G proteins. Included here is RGS4 for which a number of pharmacological inhibitors have been described.

556The RZ family of RGS proteins is less well characterized than the other families [http://www.ncbi.nlm.nih.gov/pubmed/16765607?dopt=AbstractPlus]. It consists of RGS17 (also known as RGSZ2), RGS19 (also known as GAIP) and RGS20 (with several splice variants including RGSZ1 and Ret‐RGS). All members contain an N‐terminal cysteine string motif [http://www.ncbi.nlm.nih.gov/pubmed/17183362?dopt=AbstractPlus] which is a site of palmitoylation and could serve functions in membrane targeting, protein stability or aid protein‐protein interactions [http://www.ncbi.nlm.nih.gov/pubmed/17126529?dopt=AbstractPlus]. However, the function in the case of RZ family RGS proteins is not yet fully understood. Members of the RZ family of RGS proteins are the only RGS proteins that have selective GTPase activating‐protein (GAP) activity for Gαz, a function that resulted in the name of the family [http://www.ncbi.nlm.nih.gov/pubmed/9748279?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/15096504?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9748280?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/1347957?dopt=AbstractPlus]. However, the members of the RZ family are able to also GAP Gαi/o members with varying selectivity.

557This is the largest family of RGS proteins.

558This family of RGS proteins shows some selectivity for Gai/o proteins.

559The R12 family consists of RGS10, 12 and 14. RGS12 and 14 are large proteins with additional domains that can participate in protein‐protein interactions and other functions. In contrast, RGS10 is a small protein consisting of the RGS domain and small N‐ and C‐termini, similar to members of the R4 family. However, sequence homology of the RGS10 RGS domain clearly places it in the R12 family [http://www.ncbi.nlm.nih.gov/pubmed/26123306?dopt=AbstractPlus]. The Gαi/o‐Loco (GoLoco) motif in RGS12 and 14 has GDI activity (for Guanine nucleotide Dissociation Inhibitor) towards Gαi1, Gαi2 and Gαi3 [http://www.ncbi.nlm.nih.gov/pubmed/11387333?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/15951850?dopt=AbstractPlus]. Through this activity RGS12 and RGS14 can inhibit G protein signaling both by accelerating GTP hydrolysis and by preventing G protein activation. Splice variants of RGS12 and RGS14 also contain membrane targeting and protein‐protein interaction domains [http://www.ncbi.nlm.nih.gov/pubmed/11130074?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/11771424?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9651375?dopt=AbstractPlus].

560Alqinyah M et al. (2018) Regulating the regulators: Epigenetic, transcriptional, and post‐translational regulation of RGS proteins. Cell. Signal. 42: 77‐87 [https://www.ncbi.nlm.nih.gov/pubmed/29042285?dopt=AbstractPlus]

561Neubig RR et al. (2002) Regulators of G‐protein signalling as new central nervous system drug targets. Nat Rev Drug Discov 1: 187‐97 [https://www.ncbi.nlm.nih.gov/pubmed/12120503?dopt=AbstractPlus]

562Sethakorn N et al. (2010) Non‐canonical functions of RGS proteins. Cell. Signal. 22: 1274‐81 [https://www.ncbi.nlm.nih.gov/pubmed/20363320?dopt=AbstractPlus]

563Sjögren B. (2017) The evolution of regulators of G protein signalling proteins as drug targets ‐ 20 years in the making: IUPHAR Review 21. Br. J. Pharmacol. 174: 427‐437 [https://www.ncbi.nlm.nih.gov/pubmed/28098342?dopt=AbstractPlus]

564Sjögren B et al. (2010) Thinking outside of the ‘RGS box’: new approaches to therapeutic targeting of regulators of G protein signaling. Mol. Pharmacol. 78: 550‐7 [https://www.ncbi.nlm.nih.gov/pubmed/20664002?dopt=AbstractPlus]

565Although termed ’receptors’, the evidence for coupling through conventional signalling pathways is lacking. Initially described as a subtype of opioid receptors, there is only a modest pharmacological overlap and no structural convergence with the G protein‐coupled receptors; the crystal structure of the sigma1 receptor [http://www.ncbi.nlm.nih.gov/pubmed/27042935?dopt=AbstractPlus] suggests a trimeric structure of a single short transmembrane domain traversing the endoplasmic reticulum membrane, with the bulk of the protein facing the cytosol. A wide range of compounds, ranging from psychoactive agents to antihistamines, have been observed to bind to these sites.

566http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1606 also shows activity at opioid receptors. The sigma2 receptor has recently been reported to be http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2553 [http://www.ncbi.nlm.nih.gov/pubmed/28559337?dopt=AbstractPlus], a 4TM protein partner of NPC1, the Niemann‐Pick C1 protein, a 13TM cholesterol‐binding protein.

567Chu UB et al. (2016) Biochemical Pharmacology of the Sigma‐1 Receptor. Mol. Pharmacol. 89: 142‐53 [https://www.ncbi.nlm.nih.gov/pubmed/26560551?dopt=AbstractPlus]

568Gris G et al. (2015) Sigma‐1 receptor and inflammatory pain. Inflamm. Res. 64: 377‐81 [https://www.ncbi.nlm.nih.gov/pubmed/25902777?dopt=AbstractPlus]

569Rousseaux CG et al. (2016) Sigma receptors [σRs]: biology in normal and diseased states. J. Recept. Signal Transduct. Res. 36: 327‐388 [https://www.ncbi.nlm.nih.gov/pubmed/26056947?dopt=AbstractPlus]

570Sambo DO et al. (2018) The sigma‐1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction. Pharmacol Ther 186: 152‐167 [https://www.ncbi.nlm.nih.gov/pubmed/29360540]

571Su TP et al. (2016) The Sigma‐1 Receptor as a Pluripotent Modulator in Living Systems. Trends Pharmacol. Sci. 37: 262‐278 [https://www.ncbi.nlm.nih.gov/pubmed/26869505?dopt=AbstractPlus]

572Vavers E et al. (2019) Allosteric Modulators of Sigma‐1 Receptor: A Review. Front Pharmacol 10: 223 [https://www.ncbi.nlm.nih.gov/pubmed/30941035]

573Tubulins are a family of intracellular proteins most commonly associated with microtubules, part of the cytoskeleton. They are exploited for therapeutic gain in cancer chemotherapy as targets for agents derived from a variety of natural products: taxanes, colchicine and vinca alkaloids. These are thought to act primarily through β‐tubulin, thereby interfering with the normal processes of tubulin polymer formation and disassembly.

574Arnst KE et al. (2019) Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy. Med Res Rev 39: 1398‐1426 [https://www.ncbi.nlm.nih.gov/pubmed/30746734]

575Eshun‐Wilson L. (2019) Effects of alpha‐tubulin acetylation on microtubule structure and stability. Proc Natl Acad Sci U S A 116: 10366‐10371 [https://www.ncbi.nlm.nih.gov/pubmed/31072936]

576Gadadhar S et al. (2017) The tubulin code at a glance. J. Cell. Sci. 130: 1347‐1353 [https://www.ncbi.nlm.nih.gov/pubmed/28325758?dopt=AbstractPlus]

577Magiera MM et al. (2018) Tubulin Posttranslational Modifications and Emerging Links to Human Disease. Cell 173: 1323‐1327 [https://www.ncbi.nlm.nih.gov/pubmed/29856952]

578Penna LS et al. (2017) Anti‐mitotic agents: Are they emerging molecules for cancer treatment? Pharmacol. Ther. 173: 67‐82 [https://www.ncbi.nlm.nih.gov/pubmed/28174095?dopt=AbstractPlus]