Target Information

Target General Information

Top

Target ID

T99799 (Former ID: TTDS00143)

Target Name

Cholinesterase (BCHE)

Synonyms

Pseudocholinesterase; Choline esterase II; CHE1; Butyrylcholine esterase; Acylcholine acylhydrolase

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Gene Name

BCHE

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Pain [ICD-11: MG30-MG3Z]

Tonus and reflex abnormality [ICD-11: MB47]

Function

Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.

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BioChemical Class

Type-B carboxylesterase/lipase

UniProt ID

CHLE_HUMAN

EC Number

EC 3.1.1.8

Sequence

MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIP
YAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDC
LYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG
FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPG
SHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEI
LLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVY
GAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDV
VGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER
RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMT
KLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCV
GL

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3D Structure

Click to Show 3D Structure of This Target

PDB

ADReCS ID

BADD_A00300 ; BADD_A00362 ; BADD_A01261 ; BADD_A01322 ; BADD_A02053 ; BADD_A04623

HIT2.0 ID

T25Y64

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 2 Approved Drugs

Hexafluronium bromide

Drug Info

Approved

Spasm

[2], [3]

MEPTAZINOL

Drug Info

Approved

Pain

[2]

Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

(-)-Phenserine

Drug Info

Phase 3

Alzheimer disease

[4]

Eptastigmine

Drug Info

Phase 3

Cognitive impairment

[5]

JES-9501

Drug Info

Phase 1

Alzheimer disease

[6]

Plasma derived human butyrylcholinesterase

Drug Info

Phase 1

Neurotoxicity

[7]

Protexia

Drug Info

Phase 1

Alzheimer disease

[8]

RVT-103+RVT-104

Drug Info

Phase 1

Alzheimer disease

[9]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 233 Inhibitor drugs

Hexafluronium bromide

Drug Info

[1]

MEPTAZINOL

Drug Info

[10]

(-)-Phenserine

Drug Info

[11]

Eptastigmine

Drug Info

[12]

RVT-103+RVT-104

Drug Info

[9]

Decyle nelycorine dibromo salt derivative 1

Drug Info

[15]

Di-substituted piperidine derivative 1

Drug Info

[15]

Di-substituted piperidine derivative 2

Drug Info

[15]

Di-substituted piperidine derivative 3

Drug Info

[15]

Egonol compound 1

Drug Info

[16]

Indoline derivative 1

Drug Info

[15]

Isochroman-4-ketone derivative 1

Drug Info

[15]

PMID29757691-Compound-10

Drug Info

[15]

PMID29757691-Compound-2a

Drug Info

[15]

PMID29757691-Compound-2a-i

Drug Info

[15]

PMID29757691-Compound-7

Drug Info

[15]

PMID29757691-Compound-8a

Drug Info

[15]

PMID29757691-Compound-8b

Drug Info

[15]

PMID29757691-Compound-8c

Drug Info

[15]

PMID29757691-Compound-8d

Drug Info

[15]

Quinazoline alkaloid derivative 1

Drug Info

[15]

Tacrine heterodimer derivative 1

Drug Info

[15]

Tetra-hydro-isoquinoline derivative 1

Drug Info

[15]

Tetra-hydro-isoquinoline derivative 2

Drug Info

[15]

Tetra-hydro-isoquinoline derivative 3

Drug Info

[15]

Tetra-hydro-isoquinoline derivative 4

Drug Info

[15]

(-)-DEBROMOFLUSTRAMINE B

Drug Info

[17]

(-)-Phenethylcymserine

Drug Info

[11]

(-)-Tolserine

Drug Info

[11]

(1'H-Phenothiazin-1'-yl)(piperidin-1-yl)methanone

Drug Info

[18]

(10H-phenothiazin-10-yl)(m-tolyl)methanone

Drug Info

[19]

(10H-phenothiazin-10-yl)(o-tolyl)methanone

Drug Info

[19]

(10H-phenothiazin-10-yl)(p-tolyl)methanone

Drug Info

[19]

(10H-phenothiazin-10-yl)(phenyl)methanone

Drug Info

[19]

(1R)-MENTHYL HEXYL PHOSPHONATE GROUP

Drug Info

[20]

(1S)-MENTHYL HEXYL PHOSPHONATE GROUP

Drug Info

[20]

(24S)-ethylcholesta-7,9(11),22(E)-triene-3b-ol

Drug Info

[21]

(3-bromophenyl)(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

(4-bromophenyl)(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

(4-nitrophenyl)(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

(RS)-tacrine(10)-hupyridone

Drug Info

[22]

1,10-bis(pyridinium)-decane dibromide

Drug Info

[23]

1,11-bis(pyridinium)-undecane dibromide

Drug Info

[23]

1,2-bis(2,3-fluorophenyl)ethane-1,2-dione

Drug Info

[24]

1,2-di(10H-phenothiazin-10-yl)ethane-1,2-dione

Drug Info

[19]

1,2-Di(berberine-9-O-yl)ethane dibromide

Drug Info

[25]

1,2-indanedione

Drug Info

[26]

1,2-NAPHTHOQUINONE

Drug Info

[26]

1,3-Di(berberine-9-O-yl)ethane dibromide

Drug Info

[25]

1,4-Di(berberine-9-O-yl)ethane dibromide

Drug Info

[25]

1,9-bis(pyridinium)-nonane dibromide

Drug Info

[23]

1-(10H-phenothiazin-10-yl)-2-phenylbutan-1-one

Drug Info

[19]

1-(10H-phenothiazin-10-yl)-2-phenylethanone

Drug Info

[19]

1-(10H-phenothiazin-10-yl)-2-phenylpropan-1-one

Drug Info

[19]

1-(10H-phenothiazin-10-yl)-3-phenylbutan-1-one

Drug Info

[19]

1-(10H-phenothiazin-10-yl)-3-phenylpropan-1-one

Drug Info

[19]

1-(10H-phenothiazin-10-yl)-4-phenylbutan-1-one

Drug Info

[19]

1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione

Drug Info

[27]

1-methyl-3-(phenylcarbamoyloxy)pyridinium bromide

Drug Info

[11]

2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-imine

Drug Info

[28]

2-(N-Morpholino)-Ethanesulfonic Acid

Drug Info

[29]

2-biphenyl-4-yl-1-phenothiazin-10-yl-ethanone

Drug Info

[19]

2-methoxyphenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

2-Methyl-beta-carboline-2-ium iodide

Drug Info

[31]

2-Propyl-beta-carboline-2-ium iodide

Drug Info

[31]

24-ethyl-cholest-7-ene-3,5,6-triol

Drug Info

[21]

24-ethylcholest-6-ene-3,5-diol

Drug Info

[21]

3,4,5,6-Tetrachloro-[1,2]benzoquinone

Drug Info

[32]

3-(2-Diethylamino-acetamino)-rutaecarpine

Drug Info

[33]

3-(2-Diethylamino-propionamino)-rutaecarpine

Drug Info

[33]

3-(2-N-Piperidyl-propionamino)-rutaecarpine

Drug Info

[33]

3-(2-N-Pyrrolyl-acetamino)-rutaecarpine

Drug Info

[33]

3-(2-N-Pyrrolyl-propionamino)-rutaecarpine

Drug Info

[33]

3-(dimethylamino)phenyl phenylcarbamate

Drug Info

[11]

3-chlorophenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

3-isopr-sal-cyclosal-d4TMP

Drug Info

[34]

3-methoxyphenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

3-phenyl-cyclosal-d4TMP

Drug Info

[34]

3-sal-cyclosal-d4TMP

Drug Info

[34]

3-[10-(benzylmethylamino)decyloxy]xanthen-9-one

Drug Info

[35]

3-[11-(benzylmethylamino)undecyloxy]xanthen-9-one

Drug Info

[35]

3-[12-(benzylmethylamino)dodecyloxy]xanthen-9-one

Drug Info

[35]

3-[3-(benzylmethylamino)propoxy]xanthen-9-one

Drug Info

[35]

3-[4-(benzylmethylamino)butoxy]xanthen-9-one

Drug Info

[35]

3-[5-(benzylmethylamino)pentyloxy]xanthen-9-one

Drug Info

[35]

3-[6-(benzylmethylamino)hexyloxy]xanthen-9-one

Drug Info

[35]

3-[7-(benzylmethylamino)-heptyloxy]xanthen-9-one

Drug Info

[35]

3-[8-(benzylmethylamino)octyloxy]xanthen-9-one

Drug Info

[35]

3-[9-(benzylmethylamino)nonyloxy]xanthen-9-one

Drug Info

[35]

4-chlorophenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

4-ISOPROPYLPHENSERINE

Drug Info

[36], [37]

4-methoxyphenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

4-[4-(benzyloxy)piperidino]butyl benzoate

Drug Info

[38]

4-[4-(benzyloxy)piperidino]butyl-3-chlorobenzoate

Drug Info

[38]

4-[4-(benzyloxy)piperidino]butyl-3-fluorobenzoate

Drug Info

[38]

4-[4-(benzyloxy)piperidino]butyl-4-chlorobenzoate

Drug Info

[38]

4-[4-(benzyloxy)piperidino]butyl-4-fluorobenzoate

Drug Info

[38]

4-[4-(benzyloxy)piperidino]butyl-4-nitrobenzoate

Drug Info

[38]

5,6-dinitroacenaphthoquinone

Drug Info

[26]

100

5-methyl-cyclosal-d4TMP

Drug Info

[34]

101

6-chlorotacrine hydrochloride

Drug Info

[39]

102

6-hydroxy-1,2,9-trimethyl-9H-beta-carbolin-2-ium

Drug Info

[40]

103

6-hydroxy-1,2-dimethyl-9H-beta-carbolin-2-ium

Drug Info

[40]

104

6-hydroxy-2-methyl-9H-beta-carbolin-2-ium

Drug Info

[40]

105

6-methoxy-1,2-dimethyl-9H-beta-carbolin-2-ium

Drug Info

[40]

106

6-methoxy-1,9-dimethyl-9H-pyrido[3,4-b]indole

Drug Info

[40]

107

6-methoxy-2-methyl-9H-beta-carbolin-2-ium

Drug Info

[40]

108

7-Oxo-7H-dibenzo[de,g]quinoline

Drug Info

[41]

109

9-(3-IODOBENZYLAMINO)-1,2,3,4-TETRAHYDROACRIDINE

Drug Info

[20]

110

9-Ethyl-2-methyl-beta-carboline-2-ium iodide

Drug Info

[31]

111

9-N-Phenylmethylamino-Tacrine

Drug Info

[29]

112

9-O-[2-(Phenylol-1-yloxy)ethyl]berberine bromide

Drug Info

[42]

113

9-O-[2-(Phenylol-1-yloxy)hexyl]berberine bromide

Drug Info

[42]

114

9-O-[3-(2-Pyridinoxyl)butyl]-berberine bromide

Drug Info

[25]

115

9-O-[3-(4-Bromo-phenoxyl)butyl]-berberine bromide

Drug Info

[25]

116

9-O-[3-(4-Nitro-phenoxyl)butyl]-berberine bromide

Drug Info

[25]

117

9-O-[3-(Phenylamino)propyl]-berberine bromide

Drug Info

[25]

118

9-O-[3-(Phenylol-1-yloxy)propyl]berberine bromide

Drug Info

[42]

119

9-O-[4-(Phenylol-1-yloxy)butyl]berberine bromide

Drug Info

[42]

120

9-O-[5-(Phenylol-1-yloxy)pentyl]berberine bromide

Drug Info

[42]

121

9-[5-(beta-Carboline-9-yl)pentyl]-beta-carboline

Drug Info

[31]

122

9-[9-(beta-Carboline-9-yl)nonyl]-beta-carboline

Drug Info

[31]

123

ACENAPHTHOQUINONE

Drug Info

[26]

124

Alpha-D-Mannose

Drug Info

[29]

125

Anthracen-10-yl(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

126

AS-1397

Drug Info

[43]

127

BENZOQUINONE

Drug Info

[32]

128

Beta-D-Mannose

Drug Info

[29]

129

Bis-7-tacrine

Drug Info

[44]

130

Bis-cyclosal-d4TMP

Drug Info

[34]

131

Butanoic Acid

Drug Info

[29]

132

Butyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

133

Butyrylthiocholine

Drug Info

[45]

134

CAPROCTAMINE

Drug Info

[46]

135

CHF-2819

Drug Info

[47]

136

CHLORANIL

Drug Info

[32]

137

Cyclopentyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

138

Cyclosal-d4TMP

Drug Info

[34]

139

DEMETHYLDEBROMOFLUSTRAMINE B

Drug Info

[17]

140

Diethylphosphono Group

Drug Info

[29]

141

Dodecanesulfonate ion

Drug Info

[20]

142

Ethyl Dihydrogen Phosphate

Drug Info

[29]

143

ETHYL HYDROGEN DIETHYLAMIDOPHOSPHATE

Drug Info

[20]

144

Fucose

Drug Info

[29]

145

HALOXYSTEROL A

Drug Info

[21]

146

HALOXYSTEROL B

Drug Info

[21]

147

Haloxysterol C

Drug Info

[21]

148

Haloxysterol D

Drug Info

[21]

149

Huprine X

Drug Info

[48]

150

Huprine-Tacrine Heterodimer

Drug Info

[49]

151

Iso-OMPA

Drug Info

[50]

152

Isopropyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

153

Isosorbide-2-(benzylcarbamate)-5-benzoate

Drug Info

[50]

154

Isosorbide-2-(benzylcarbamate)-5-mononitrate

Drug Info

[50]

155

Isosorbide-2-(butylcarbamate)-5-benzoate

Drug Info

[50]

156

Isosorbide-2-(butylcarbamate)-5-mononitrate

Drug Info

[50]

157

Isosorbide-2-(cyclohexylcarbamate)-5-mononitrate

Drug Info

[50]

158

Isosorbide-2-(ethylcarbamate)-5-mononitrate

Drug Info

[50]

159

Isosorbide-2-(methylcarbamate)-5-benzoate

Drug Info

[50]

160

Isosorbide-2-(methylcarbamate)-5-mononitrate

Drug Info

[50]

161

Isosorbide-2-(propylcarbamate)-5-mononitrate

Drug Info

[50]

162

Isosorbide-2-benzyl carbamate

Drug Info

[51]

163

Isosorbide-2-benzylcarbamate-5-(o-toluate)

Drug Info

[51]

164

Isosorbide-2-benzylcarbamate-5-acetate

Drug Info

[50]

165

Isosorbide-2-benzylcarbamate-5-cyclopentanoate

Drug Info

[50]

166

Isosorbide-2-benzylcarbamate-5-cyclopropanoate

Drug Info

[50]

167

Isosorbide-2-benzylcarbamate-5-isonicotinate

Drug Info

[50]

168

Isosorbide-2-benzylcarbamate-5-nicotinate

Drug Info

[50]

169

Isosorbide-2-benzylcarbamate-5-pentanoate

Drug Info

[50]

170

Isosorbide-2-benzylcarbamate-5-propionate

Drug Info

[50]

171

Isosorbide-2-benzylcarbamate-5-triflate

Drug Info

[50]

172

Isosorbide-di-(benzylcarbamate)

Drug Info

[52]

173

Isosorbide-di-(butylcarbamate)

Drug Info

[52]

174

Isosorbide-di-(ethylcarbamate)

Drug Info

[52]

175

Isosorbide-di-(propylcarbamate)

Drug Info

[52]

176

LAWSARITOL

Drug Info

[21]

177

LIPOCRINE

Drug Info

[53]

178

M-tolyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

179

MEMOQUIN

Drug Info

[53]

180

Methyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

181

Methyl Phosphinic Acid

Drug Info

[29]

182

MF-8623

Drug Info

[36]

183

Monoisopropyl Ester Phosphonic Acid Group

Drug Info

[29]

184

Morpholino(1'H-phenothiazin-1'-yl)methanone

Drug Info

[18]

185

N,N'-(1',10'-decylene)-bis-(-)-nor-MEP

Drug Info

[10]

186

N,N'-(1',11'-undecydene)-bis-(-)-nor-MEP

Drug Info

[10]

187

N,N'-(1',12'-dodecydene)-bis-(-)-nor-MEP

Drug Info

[10]

188

N,N'-(1',2'-ethylene)-bis-(-)-nor-MEP

Drug Info

[10]

189

N,N'-(1',3'-propylene)-bis-(-)-nor-MEP

Drug Info

[10]

190

N,N'-(1',4'-butylene)-bis-(-)-nor-MEP

Drug Info

[10]

191

N,N'-(1',5'-pentylene)-bis-(-)-nor-MEP

Drug Info

[10]

192

N,N'-(1',6-hexylene)-bis-(-)-nor-MEP

Drug Info

[10]

193

N,N'-(1',7'-heptylene)-bis-(-)-nor-MEP

Drug Info

[10]

194

N,N'-(1',8'-octylene)-bis-(-)-nor-MEP

Drug Info

[10]

195

N,N'-(1',9'-nonylene)-bis-(-)-nor-MEP

Drug Info

[10]

196

N,N-Diethyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

197

N,N-Diisopropyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

198

N,N-Dimethyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

199

N,N-Dipropyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

200

N-(Adamant-1-yl)-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

201

N-Benzyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

202

N-benzyl-2-thiomorpholinopyrimidin-4-amine

Drug Info

[44]

203

N-Cyclobutyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

204

N-Cyclohexyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

205

N-Cyclopentyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

206

N-Isopropyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

207

N-Methyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

208

N-n-heptyl-7-methoxytacrine hydrochloride

Drug Info

[54]

209

N-n-hexyl-7-methoxytacrine hydrochloride

Drug Info

[54]

210

N-n-nonyl-7-methoxytacrine hydrochloride

Drug Info

[54]

211

N-n-octyl-7-methoxytacrine hydrochloride

Drug Info

[54]

212

N-n-pentyl-7-methoxytacrine hydrochloride

Drug Info

[54]

213

N-Neopentyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

214

N-o-Tolyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

215

N-p-Tolyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

216

N-phenethyl-2-(pyrrolidin-1-yl)pyrimidin-4-amine

Drug Info

[44]

217

N-Phenyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

218

N-tert-Butyl-1'H-phenothiazine-1'-carboxamide

Drug Info

[18]

219

Naphthalen-1-yl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

220

Naphthalen-1-yl(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

221

Naphthalen-2-yl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

222

Naphthalen-2-yl(10H-phenothiazin-10-yl)methanone

Drug Info

[19]

223

NOSTOCARBOLINE

Drug Info

[56]

224

NP-0336

Drug Info

[55]

225

NSC-23180

Drug Info

[26]

226

O-tolyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

227

P-tolyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

228

Phenanthrene-9,10-dione

Drug Info

[26]

229

Phenyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

230

Tert-butyl 10H-phenothiazine-10-carboxylate

Drug Info

[30]

231

TOLSERINE

Drug Info

[12]

232

VAGANINE D

Drug Info

[57]

233

XANTHOSTIGMINE

Drug Info

[58]

Modulator

[+] 5 Modulator drugs

JES-9501

Drug Info

[6]

Plasma derived human butyrylcholinesterase

Drug Info

[13]

Protexia

Drug Info

[14]

Non-PEGylated butyrylcholinesterase

Drug Info

[55]

Recombinant human butyrylcholinesterase

Drug Info

[55]

Reactivator

[+] 1 Reactivator drugs

Oxime derivative 1

Drug Info

[15]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Tacrine

Ligand Info

Structure Description

Human butyrylcholinesterase in complex with tacrine

PDB:4BDS

Method

X-ray diffraction

Resolution

2.10 Å

Mutation

Yes

[59]

PDB Sequence

IIIATKNGKV

¹³

RGMQLTVFGG

²³

TVTAFLGIPY

³³

AQPPLGRLRF

⁴³

KKPQSLTKWS

⁵³

DIWNATKYAN

⁶³

SCCQNIDQSF

⁷³

PGFHGSEMWN

⁸³

PNTDLSEDCL

⁹³

YLNVWIPAPK

¹⁰³

PKNATVLIWI

¹¹³

YGGGFQTGTS

¹²³

SLHVYDGKFL

¹³³

ARVERVIVVS

¹⁴³

MNYRVGALGF

¹⁵³

LALPGNPEAP

¹⁶³

GNMGLFDQQL

¹⁷³

ALQWVQKNIA

¹⁸³

AFGGNPKSVT

¹⁹³

LFGESAGAAS

²⁰³

VSLHLLSPGS

²¹³

HSLFTRAILQ

²²³

SGSFNAPWAV

²³³

TSLYEARNRT

²⁴³

LNLAKLTGCS

²⁵³

RENETEIIKC

²⁶³

LRNKDPQEIL

²⁷³

LNEAFVVPYG

²⁸³

TPLSVNFGPT

²⁹³

VDGDFLTDMP

³⁰³

DILLELGQFK

³¹³

KTQILVGVNK

³²³

DEGTAFLVYG

³³³

APGFSKDNNS

³⁴³

IITRKEFQEG

³⁵³

LKIFFPGVSE

³⁶³

FGKESILFHY

³⁷³

TDWVQRPENY

³⁸⁵

REALGDVVGD

³⁹⁵

YNFICPALEF

⁴⁰⁵

TKKFSEWGNN

⁴¹⁵

AFFYYFEHRS

⁴²⁵

SKLPWPEWMG

⁴³⁵

VMHGYEIEFV

⁴⁴⁵

FGLPLERRDQ

⁴⁵⁵

YTKAEEILSR

⁴⁶⁵

SIVKRWANFA

⁴⁷⁵

KYGNPQETQN

⁴⁸⁵

QSTSWPVFKS

⁴⁹⁵

TEQKYLTLNT

⁵⁰⁵

ESTRIMTKLR

⁵¹⁵

AQQCRFWTSF

⁵²⁵

FPKV

Residue

Distance (Å)

ASP70

4.386

GLY78

4.290

SER79

4.694

TRP82

3.401

GLY115

3.976

GLY116

3.925

TYR128

4.335

GLU197

3.177

Residue

Distance (Å)

SER198

4.111

ALA328

3.766

TYR332

3.520

TRP430

3.523

MET437

3.907

HIS438

3.154

GLY439

3.908

TYR440

4.098

Ligand Name: Beta-L-fucose

Ligand Info

Structure Description

Human Butyrylcholinesterase complexed with N-Propargyliperidines

PDB:5LKR

Method

X-ray diffraction

Resolution

2.52 Å

Mutation

[60]

PDB Sequence

DIIIATKNGK

¹²

VRGMNLTVFG

²²

GTVTAFLGIP

³²

YAQPPLGRLR

⁴²

FKKPQSLTKW

⁵²

SDIWNATKYA

⁶²

NSCCQNIDQS

⁷²

FPGFHGSEMW

⁸²

NPNTDLSEDC

⁹²

LYLNVWIPAP

¹⁰²

KPKNATVLIW

¹¹²

IYGGGFQTGT

¹²²

SSLHVYDGKF

¹³²

LARVERVIVV

¹⁴²

SMNYRVGALG

¹⁵²

FLALPGNPEA

¹⁶²

PGNMGLFDQQ

¹⁷²

LALQWVQKNI

¹⁸²

AAFGGNPKSV

¹⁹²

TLFGESAGAA

²⁰²

SVSLHLLSPG

²¹²

SHSLFTRAIL

²²²

QSGSFNAPWA

²³²

VTSLYEARNR

²⁴²

TLNLAKLTGC

²⁵²

SRENETEIIK

²⁶²

CLRNKDPQEI

²⁷²

LLNEAFVVPY

²⁸²

GTPLSVNFGP

²⁹²

TVDGDFLTDM

³⁰²

PDILLELGQF

³¹²

KKTQILVGVN

³²²

KDEGTAFLVY

³³²

GAPGFSKDNN

³⁴²

SIITRKEFQE

³⁵²

GLKIFFPGVS

³⁶²

EFGKESILFH

³⁷²

YTDWVDDQRP

³⁸²

ENYREALGDV

³⁹²

VGDYNFICPA

⁴⁰²

LEFTKKFSEW

⁴¹²

GNNAFFYYFE

⁴²²

HRSSKLPWPE

⁴³²

WMGVMHGYEI

⁴⁴²

EFVFGLPLER

⁴⁵²

RDNYTKAEEI

⁴⁶²

LSRSIVKRWA

⁴⁷²

NFAKYGNPNE

⁴⁸²

TQNNSTSWPV

⁴⁹²

FKSTEQKYLT

⁵⁰²

LNTESTRIMT

⁵¹²

KLRAQQCRFW

⁵²²

TSFFPKVL

Residue

Distance (Å)

ASP3

4.148

ARG14

4.002

Residue

Distance (Å)

ASN57

4.765

Click to View More Binding Site Information of This Target and Ligand Pair

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Arylacetamide deacetylase (AADAC)	PF07859	31.707 (39/123)	3.72E-05


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.71E-01	Radiality	1.27E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.30E+01	Topological coefficient	1.00E+00	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

Top

Panther Pathway

[+] 3 Panther Pathways

Muscarinic acetylcholine receptor 1 and 3 signaling pathway

Muscarinic acetylcholine receptor 2 and 4 signaling pathway

Nicotinic acetylcholine receptor signaling pathway

WikiPathways

[+] 1 WikiPathways

Irinotecan Pathway

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

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Homobivalent quinazolinimines as novel nanomolar inhibitors of cholinesterases with dirigible selectivity toward butyrylcholinesterase. J Med Chem. 2006 Sep 7;49(18):5411-3.

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Design, synthesis, evaluation and QSAR analysis of N(1)-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1718-20.

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