Target Information

Target General Information

Top

Target ID

T99347 (Former ID: TTDC00100)

Target Name

Metabotropic glutamate receptor 5 (mGluR5)

Synonyms

MGLUR5; GPRC1E

Click to Show/Hide

Gene Name

GRM5

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Fragile X chromosome [ICD-11: LD55]

Parkinsonism [ICD-11: 8A00]

Function

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Click to Show/Hide

BioChemical Class

GPCR glutamate

UniProt ID

GRM5_HUMAN

Sequence

MVLLLILSVLLLKEDVRGSAQSSERRVVAHMPGDIIIGALFSVHHQPTVDKVHERKCGAV
REQYGIQRVEAMLHTLERINSDPTLLPNITLGCEIRDSCWHSAVALEQSIEFIRDSLISS
EEEEGLVRCVDGSSSSFRSKKPIVGVIGPGSSSVAIQVQNLLQLFNIPQIAYSATSMDLS
DKTLFKYFMRVVPSDAQQARAMVDIVKRYNWTYVSAVHTEGNYGESGMEAFKDMSAKEGI
CIAHSYKIYSNAGEQSFDKLLKKLTSHLPKARVVACFCEGMTVRGLLMAMRRLGLAGEFL
LLGSDGWADRYDVTDGYQREAVGGITIKLQSPDVKWFDDYYLKLRPETNHRNPWFQEFWQ
HRFQCRLEGFPQENSKYNKTCNSSLTLKTHHVQDSKMGFVINAIYSMAYGLHNMQMSLCP
GYAGLCDAMKPIDGRKLLESLMKTNFTGVSGDTILFDENGDSPGRYEIMNFKEMGKDYFD
YINVGSWDNGELKMDDDEVWSKKSNIIRSVCSEPCEKGQIKVIRKGEVSCCWTCTPCKEN
EYVFDEYTCKACQLGSWPTDDLTGCDLIPVQYLRWGDPEPIAAVVFACLGLLATLFVTVV
FIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAMSYS
ALVTKTNRIARILAGSKKKICTKKPRFMSACAQLVIAFILICIQLGIIVALFIMEPPDIM
HDYPSIREVYLICNTTNLGVVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYT
TCIIWLAFVPIYFGSNYKIITMCFSVSLSATVALGCMFVPKVYIILAKPERNVRSAFTTS
TVVRMHVGDGKSSSAASRSSSLVNLWKRRGSSGETLRYKDRRLAQHKSEIECFTPKGSMG
NGGRATMSSSNGKSVTWAQNEKSSRGQHLWQRLSIHINKKENPNQTAVIKPFPKSTESRG
LGAGAGAGGSAGGVGATGGAGCAGAGPGGPESPDAGPKALYDVAEAEEHFPAPARPRSPS
PISTLSHRAGSASRTDDDVPSLHSEPVARSSSSQGSLMEQISSVVTRFTANISELNSMML
STAAPSPGVGAPLCSSYLIPKEIQLPTTMTTFAEIQPLPAIEVTGGAQPAAGAQAAGDAA
RESPAAGPEAAAAKPDLEELVALTPPSPFRDSVDSGSTTPNSPVSESALCIPSSPKYDTL
IIRDYTQSSSSL

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T64P00

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 9 Clinical Trial Drugs

ADX-48621

Drug Info

Phase 2/3

Parkinson disease

[2]

AFQ056

Drug Info

Phase 2/3

Fragile X syndrome

[3], [4]

ADX10059

Drug Info

Phase 2

Anxiety disorder

[5]

RG-7090

Drug Info

Phase 2

Fragile X syndrome

[6]

STX-107

Drug Info

Phase 2

Autism spectrum disorder

[7], [8]

McN3377

Drug Info

Phase 1/2

Fragile X syndrome

[9], [10]

MK-3328

Drug Info

Phase 1

Alzheimer disease

[11]

RG7342

Drug Info

Phase 1

Schizophrenia

[12]

[3H]fenobam

Drug Info

Phase 1

Allodynia

[13]

Patented Agent(s)

[+] 5 Patented Agents

Diazepinone derivative 1

Drug Info

Patented

Reflux disease

[14]

Diazepinone derivative 2

Drug Info

Patented

Reflux disease

[14]

Diazepinone derivative 3

Drug Info

Patented

Reflux disease

[14]

Diazepinone derivative 4

Drug Info

Patented

Reflux disease

[14]

Diazepinone derivative 5

Drug Info

Patented

Reflux disease

[14]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

AZD2066

Drug Info

Discontinued in Phase 2

Chronic neuropathic pain

[15]

AZD2516

Drug Info

Discontinued in Phase 2

Chronic neuropathic pain

[16]

LY467711

Drug Info

Terminated

Migraine

[17]

LY525327

Drug Info

Terminated

Migraine

[17]

Mode of Action

[+] 5 Modes of Action

Modulator

[+] 65 Modulator drugs

ADX-48621

Drug Info

[18]

AFQ056

Drug Info

[1]

ADX10059

Drug Info

[19], [20]

McN3377

Drug Info

[24]

MK-3328

Drug Info

[25]

6-aryl-imidazopyridine and 6-aryl-triazolopyridine carboxamide analog 1

Drug Info

[14]

6-aryl-imidazopyridine and 6-aryl-triazolopyridine carboxamide analog 2

Drug Info

[14]

6-aryl-imidazopyridine and 6-aryl-triazolopyridine carboxamide analog 3

Drug Info

[14]

Bicarboxylic and tricarboxylic ethynyl derivative 1

Drug Info

[14]

Bicarboxylic and tricarboxylic ethynyl derivative 2

Drug Info

[14]

Bicarboxylic and tricarboxylic ethynyl derivative 3

Drug Info

[14]

Bicyclic heteroaryl carboxamide analog 1

Drug Info

[14]

Bicyclic heteroaryl carboxamide analog 2

Drug Info

[14]

Bicyclic heteroaryl carboxamide analog 3

Drug Info

[14]

Diazepinone derivative 1

Drug Info

[14]

Diazepinone derivative 2

Drug Info

[14]

Diazepinone derivative 3

Drug Info

[14]

Diazepinone derivative 4

Drug Info

[14]

Diazepinone derivative 5

Drug Info

[14]

Ethynyl compound 1

Drug Info

[14]

Ethynyl compound 2

Drug Info

[14]

Ethynyl compound 3

Drug Info

[14]

Ethynyl compound 4

Drug Info

[14]

Ethynyl compound 5

Drug Info

[14]

Ethynyl compound 6

Drug Info

[14]

Ethynyl compound 7

Drug Info

[14]

Heterocyclic derivative 1

Drug Info

[14]

Heterocyclic derivative 2

Drug Info

[14]

Heterocyclic derivative 3

Drug Info

[14]

Imidazopyridine and triazolopyridine compound 1

Drug Info

[14]

Imidazopyridine and triazolopyridine compound 2

Drug Info

[14]

Imidazopyridine and triazolopyridine compound 3

Drug Info

[14]

Imidazopyridine and triazolopyridine compound 4

Drug Info

[14]

Imidazo[1,2-a]pyridine derivative 1

Drug Info

[14]

N-alkylamide derivative 1

Drug Info

[14]

N-alkylamide derivative 2

Drug Info

[14]

PMID28067079-Compound-95

Drug Info

[14]

PMID28067079-Compound-97

Drug Info

[14]

PMID28067079-Compound-98

Drug Info

[14]

Pyrazolopyrimidine derivative 1

Drug Info

[14]

Pyrazolopyrimidine derivative 2

Drug Info

[14]

Pyrazolopyrimidine derivative 3

Drug Info

[14]

Pyrazolopyrimidine derivative 4

Drug Info

[14]

Pyrazolopyrimidine derivative 5

Drug Info

[14]

Pyrazolopyrimidine derivative 6

Drug Info

[14]

Pyridine derivative 12

Drug Info

[14]

Pyridine derivative 13

Drug Info

[14]

Pyridine derivative 14

Drug Info

[14]

Pyridine derivative 15

Drug Info

[14]

Pyridine derivative 16

Drug Info

[14]

Pyridine derivative 17

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 1

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 2

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 3

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 4

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 5

Drug Info

[14]

Tetra-hydro-oxazolopyridine derivative 6

Drug Info

[14]

Tetra-hydro-pyrazolopyrazine derivative 1

Drug Info

[14]

Tetra-hydro-pyrazolopyrazine derivative 2

Drug Info

[14]

Tetra-hydro-pyrazolopyrazine derivative 3

Drug Info

[14]

Tetra-hydro-pyrazolopyrazine derivative 4

Drug Info

[14]

Tetra-hydro-pyrazolopyrazine derivative 5

Drug Info

[14]

ADX-63365

Drug Info

[25]

GRN-529

Drug Info

[25]

LY-3390334

Drug Info

[68]

Antagonist

[+] 17 Antagonist drugs

RG-7090

Drug Info

[21]

STX-107

Drug Info

[22], [23]

2-(substituted ethynyl)quinoline derivative 1

Drug Info

[14]

2-(substituted ethynyl)quinoline derivative 2

Drug Info

[14]

2-(substituted ethynyl)quinoline derivative 3

Drug Info

[14]

2-(substituted ethynyl)quinoline derivative 4

Drug Info

[14]

AZD2066

Drug Info

[28]

AZD2516

Drug Info

[28]

LY467711

Drug Info

[24]

LY525327

Drug Info

[24]

(+)-MCPG

Drug Info

[29]

(S)-4C3HPG

Drug Info

[29]

(S)-4CPG

Drug Info

[29]

ACDPP

Drug Info

[62]

CTEP

Drug Info

[25], [66]

GSK-2210875

Drug Info

[25]

RTI-4229-982

Drug Info

[25]

Agonist

[+] 8 Agonist drugs

RG7342

Drug Info

[26]

(1S,3R)-ACPD

Drug Info

[29]

(S)-(+)-CBPG

Drug Info

[34]

(S)-3HPG

Drug Info

[29]

3,5-DHPG

Drug Info

[29]

CHPG

Drug Info

[29]

ibotenate

Drug Info

[29]

L-CCG-I

Drug Info

[29]

Modulator (allosteric modulator)

[+] 51 Modulator (allosteric modulator) drugs

[3H]fenobam

Drug Info

[27]

3,3'-difluorobenzaldazine

Drug Info

[49]

5-MPEP

Drug Info

[59]

5PAM523

Drug Info

[60]

alloswitch-1

Drug Info

[63]

BOMA

Drug Info

[57]

Br-5MPEPy

Drug Info

[59]

CPPHA

Drug Info

[64]

CPPZ

Drug Info

[65]

LSN2463359

Drug Info

[67]

LSN2814617

Drug Info

[67]

M-5MPEP

Drug Info

[59]

NCFP

Drug Info

[71]

PMID14697765C11a

Drug Info

[57]

PMID14697765C16a

Drug Info

[57]

PMID15482906C10

Drug Info

[72]

PMID15482908C8

Drug Info

[73]

PMID15686941C13

Drug Info

[62]

PMID16439120C20

Drug Info

[39]

PMID16439120C26

Drug Info

[39]

PMID17189691C42

Drug Info

[74]

PMID17723296C18

Drug Info

[37]

PMID17936624C36

Drug Info

[36]

PMID19931453C16m

Drug Info

[61]

PMID20598884C8

Drug Info

[54]

PMID20809633C29b

Drug Info

[75]

PMID21295468C47

Drug Info

[76]

PMID21757343C30

Drug Info

[77]

PMID21927650C18

Drug Info

[78]

PMID23357634C24d

Drug Info

[79]

PMID23374867C24

Drug Info

[80]

PMID23434029C41

Drug Info

[81]

PMID23434029C53

Drug Info

[81]

PTeB

Drug Info

[50]

SP203

Drug Info

[82]

VU-1545

Drug Info

[56]

VU0092273

Drug Info

[83]

VU0240382

Drug Info

[83]

VU0285683

Drug Info

[84]

VU0357121

Drug Info

[85]

VU0360172

Drug Info

[84]

VU0361747

Drug Info

[83]

VU0364289

Drug Info

[86]

VU0366058

Drug Info

[87]

VU0404251

Drug Info

[88]

VU0424465

Drug Info

[89]

VU0463841

Drug Info

[90]

[14C]MTEP

Drug Info

[91]

[3H]methoxy-PEPy

Drug Info

[92]

[3H]methoxymethyl-MTEP

Drug Info

[91], [92]

[3H]resolvin E1

Drug Info

[30]

Inhibitor

[+] 197 Inhibitor drugs

(3-(2-methylquinolin-7-yl)phenyl)methanol

Drug Info

[30]

(3-Ethoxy-pyridin-2-yl)-pyridin-2-yl-amine

Drug Info

[31]

(E)-1-Adamantan-1-yl-3-quinolin-3-yl-propenone

Drug Info

[32]

(E)-3-[2-(2-methyl-4-thiazolyl)vinyl]pyridine

Drug Info

[33]

1-(3-(2-methylquinolin-7-yl)phenyl)ethanone

Drug Info

[30]

2-(2-Methyl-thiazol-4-ylethynyl)-pyridine

Drug Info

[35]

2-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

2-(3,4-dimethylphenyl)-1,8-naphthyridine

Drug Info

[36]

2-(3,5-dichlorophenyl)pyrido[2,3-d]pyrimidine

Drug Info

[37]

2-(3,5-difluorophenyl)-7-methyl-1,8-naphthyridine

Drug Info

[36]

2-(3,5-dimethoxyphenyl)-1,8-naphthyridine

Drug Info

[36]

2-(3-(2-methylquinolin-7-yl)phenyl)acetonitrile

Drug Info

[30]

2-(3-(3-methoxyphenoxy)prop-1-ynyl)pyridine

Drug Info

[38]

2-(3-(benzyloxy)phenyl)isoindoline-1,3-dione

Drug Info

[39]

2-(3-bromophenyl)-7-methyl-1,8-naphthyridine

Drug Info

[36]

2-(3-bromophenyl)-7-methylpyrido[2,3-d]pyrimidine

Drug Info

[37]

2-(3-bromophenyl)pyrido[2,3-d]pyrimidine

Drug Info

[37]

2-(3-chlorobenzyloxy)-6-chloroisonicotinonitrile

Drug Info

[39]

2-(3-chlorophenyl)-7-methyl-1,8-naphthyridine

Drug Info

[36]

2-(4-(3-chlorophenyl)but-1-ynyl)-6-methylpyridine

Drug Info

[40]

2-(m-tolylethynyl)pyrimidine

Drug Info

[41]

2-(phenylethynyl)pyrimidine

Drug Info

[41]

2-(pyridin-2-yl)-4-(m-tolylthio)pyrimidine

Drug Info

[42]

2-Benzoxy-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[23]

2-benzyloxy-7,8-dihydro-6H-quinolin-5-one

Drug Info

[43]

2-bromo-4-(3-fluorophenylethynyl)thiazole

Drug Info

[33]

2-Chloro-5-(2-methylquinolin-7-yl)nicotinonitrile

Drug Info

[23]

2-chloro-N-(3-(3-chlorobenzamido)phenyl)benzamide

Drug Info

[44]

2-Cyclohex-1-enylethynyl-pyridine

Drug Info

[45]

2-Cyclohexylethynyl-pyridine

Drug Info

[45]

2-Cyclopent-1-enylethynyl-pyridine

Drug Info

[45]

2-ethoxy-5-(m-tolylethynyl)pyrimidine

Drug Info

[41]

2-ethynyl-4-(3-fluorophenylethynyl)thiazole

Drug Info

[33]

2-m-tolyl-1,8-naphthyridine

Drug Info

[36]

2-methyl-4-(2-thienylethynyl)thiazole

Drug Info

[33]

2-methyl-4-(3-thienylethynyl)thiazole

Drug Info

[33]

2-methyl-4-(m-tolylethynyl)thiazole

Drug Info

[33]

2-Methyl-4-o-tolylethynyl-thiazole

Drug Info

[35]

2-Methyl-4-p-tolylethynyl-thiazole

Drug Info

[35]

2-Methyl-4-phenylethynyl-thiazole

Drug Info

[35]

2-methyl-6-(3-(p-tolyloxy)prop-1-ynyl)pyridine

Drug Info

[38]

2-methyl-6-(3-(phenylthio)prop-1-ynyl)pyridine

Drug Info

[40]

2-methyl-6-(4-phenylbut-1-ynyl)pyridine

Drug Info

[40]

2-methyl-6-(4-phenylpent-1-ynyl)pyridine

Drug Info

[40]

2-methyl-6-(5-phenylpent-1-ynyl)pyridine

Drug Info

[40]

2-methyl-6-(phenylethynyl)pyridine

Drug Info

[46], [47]

2-methyl-7-(pyridin-3-yl)quinoline

Drug Info

[30]

2-methyl-7-m-tolyl-1,6-naphthyridine

Drug Info

[36]

2-methyl-7-m-tolyl-1,8-naphthyridine

Drug Info

[36]

2-methyl-7-m-tolylquinoline

Drug Info

[30]

2-methyl-7-phenyl-1,8-naphthyridine

Drug Info

[36]

2-methyl-7-phenylquinoline

Drug Info

[30]

2-phenyl-1,8-naphthyridine

Drug Info

[36]

2-Phenyl-5-(2-methylthiazol-4ylethynyl)pyridine

Drug Info

[48]

2-phenylethynyl-5,6,7,8-tetrahydro-quinolin-5-ol

Drug Info

[43]

2-phenylethynyl-5,6,7,8-tetrahydro-quinoline

Drug Info

[43]

2-phenylethynyl-7,8-dihydro-6H-quinolin-5-one

Drug Info

[43]

2-[(2-methyl-4-thiazolyl)ethynyl]pyrazine

Drug Info

[33]

3-(1,5-naphthyridin-3-yl)benzonitrile

Drug Info

[36]

3-(1,8-naphthyridin-2-yl)benzonitrile

Drug Info

[36]

3-(1-Pyridin-2-yl-1H-pyrazol-3-yl)-benzonitrile

Drug Info

[50]

3-(1-Pyridin-2-yl-1H-pyrazol-4-yl)-benzonitrile

Drug Info

[50]

3-(1-Pyridin-2-yl-1H-pyrrol-3-yl)-benzonitrile

Drug Info

[50]

3-(2-methylbenzo[d]thiazol-5-yl)benzonitrile

Drug Info

[51]

3-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

3-(2-methylquinolin-7-yl)phenol

Drug Info

[30]

3-(2-Pyridin-2-yl-2H-tetrazol-5-yl)-benzonitrile

Drug Info

[50]

3-(3,4-dimethylphenyl)-1,5-naphthyridine

Drug Info

[36]

3-(3-(3-chlorobenzyloxy)-5-methylphenyl)pyridine

Drug Info

[39]

3-(3-bromophenylethynyl)-5-methyl[1,2,4]triazine

Drug Info

[52]

3-(3-methylphenylethynyl)-5-methyl[1,2,4]triazine

Drug Info

[52]

3-(3-Pyridin-2-yl-pyrazol-1-yl)-benzonitrile

Drug Info

[50]

3-(3-Pyridin-2-yl-pyrrol-1-yl)-benzonitrile

Drug Info

[50]

3-(4-Pyridin-2-yl-imidazol-1-yl)-benzonitrile

Drug Info

[50]

3-(4-Pyridin-2-yl-pyrazol-1-yl)-benzonitrile

Drug Info

[50]

3-(5-Pyridin-2-yl-tetrazol-2-yl)-benzonitrile

Drug Info

[50]

3-(6-fluoroquinazolin-4-ylamino)benzonitrile

Drug Info

[47]

3-(7-methyl-1,8-naphthyridin-2-yl)benzonitrile

Drug Info

[36]

3-biphenyl-4-ylethynyl-5-methyl-[1,2,4]triazine

Drug Info

[52]

3-bromo-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

3-bromo-5-[(2-methyl-4-thiazolyl)ethynyl]pyridine

Drug Info

[33]

3-bromo-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[53]

3-chloro-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

3-chloro-N-(3-isobutyramidophenyl)benzamide

Drug Info

[44]

3-chloro-N-(4-methylthiazol-2-yl)benzamide

Drug Info

[53]

3-chloro-N-(6-chloropyridin-2-yl)benzamide

Drug Info

[53]

3-chloro-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[48]

3-cyano-5-fluoro-N-(3-fluorophenyl)benzamide

Drug Info

[54]

3-cyano-5-fluoro-N-(pyridin-2-yl)benzamide

Drug Info

[54]

3-cyano-5-fluoro-N-m-tolylbenzamide

Drug Info

[54]

3-cyano-5-fluoro-N-phenylbenzamide

Drug Info

[54]

3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[55], [56]

3-cyano-N-(1,4-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[56]

3-cyano-N-(3-cyanophenyl)-5-fluorobenzamide

Drug Info

[54]

3-cyano-N-(3-ethylphenyl)-5-fluorobenzamide

Drug Info

[54]

3-cyano-N-(3-ethynylphenyl)-5-fluorobenzamide

Drug Info

[54]

3-cyano-N-(6-ethylpyridin-2-yl)-5-fluorobenzamide

Drug Info

[54]

3-cyano-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[48]

3-ethoxy-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

100

3-fluoro-5-(1,6-naphthyridin-7-yl)benzonitrile

Drug Info

[36]

101

3-fluoro-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

102

3-hydroxy-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

103

3-iodo-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[53]

104

3-isobutoxy-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

105

3-m-tolyl-1,5-naphthyridine

Drug Info

[36]

106

3-methoxy-5-(1,5-naphthyridin-3-yl)benzonitrile

Drug Info

[36]

107

3-methoxy-5-(1,6-naphthyridin-7-yl)benzonitrile

Drug Info

[36]

108

3-methoxy-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

109

3-methoxy-N-(4-methylthiazol-2-yl)benzamide

Drug Info

[53]

110

3-methoxy-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[53]

111

3-methyl-5-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[30]

112

3-methyl-N-(6-methylpyridin-2-yl)benzamide

Drug Info

[53]

113

3-nitro-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[56]

114

3-Phenyl-1-(2-methylthiazol-4-ylethynyl)benzene

Drug Info

[48]

115

3-[(2,5-dimethyl-4-thiazolyl)ethynyl]pyridine

Drug Info

[33]

116

3-[(2-methyl-4-thiazolyl)ethynyl]-5-vinylpyridine

Drug Info

[33]

117

3-[(2-methyl-4-thiazolyl)ethynyl]benzamide

Drug Info

[33]

118

3-[(2-methyl-4-thiazolyl)ethynyl]benzonitrile

Drug Info

[33], [57]

119

3-[(2-methyl-4-thiazolyl)ethynyl]phenol

Drug Info

[33]

120

3-[(5-ethyl-2-methyl-4-thiazolyl)ethynyl]pyridine

Drug Info

[33]

121

3-[(6-Methylpyridin-2-yl)ethynyl]benzonitrile

Drug Info

[48]

122

4-(2-(3-fluorophenyl)ethynyl)-2-methylthiazole

Drug Info

[33]

123

4-(2-(4-fluorophenyl)ethynyl)-2-methylthiazole

Drug Info

[33]

124

4-(2-fluorophenylethynyl)-2-methylthiazole

Drug Info

[33]

125

4-(2-methoxyphenylethynyl)-2-methylthiazole

Drug Info

[33]

126

4-(2-Methyl-thiazol-4-ylethynyl)-pyridine

Drug Info

[35]

127

4-(3,5-difluorophenylethynyl)-2-methylthiazole

Drug Info

[33]

128

4-(3-bromophenoxy)-6-chloroquinazoline

Drug Info

[47]

129

4-(3-bromophenylthio)-2-(pyridin-2-yl)pyrimidine

Drug Info

[42]

130

4-(3-chlorophenylethynyl)-2-methylthiazole

Drug Info

[33]

131

4-(3-chlorophenylthio)-2-(pyridin-2-yl)pyrimidine

Drug Info

[42]

132

4-(3-fluorophenylethynyl)-2-thiazolylamine

Drug Info

[33]

133

4-(3-methoxyphenylethynyl)-2-methylthiazole

Drug Info

[33]

134

4-(3-pyridylethynyl)-2-thiazolylamine

Drug Info

[33]

135

4-(4-chlorophenylthio)-2-(pyridin-2-yl)pyrimidine

Drug Info

[42]

136

4-Biphenyl-2-ylethynyl-2-methyl-thiazole

Drug Info

[35]

137

4-Biphenyl-4-ylethynyl-2-methyl-thiazole

Drug Info

[35]

138

4-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[56]

139

5-((6-Methylpyridin-2-yl)ethynyl)nicotinonitrile

Drug Info

[23]

140

5-(2-(2,5-dimethylphenyl)ethynyl)pyrimidine

Drug Info

[58]

141

5-(2-(3,5-difluorophenyl)ethynyl)pyrimidine

Drug Info

[58]

142

5-(2-(3-chlorophenyl)ethynyl)pyrimidine

Drug Info

[58]

143

5-(2-(4-fluoro-3-methylphenyl)ethynyl)pyrimidine

Drug Info

[58]

144

5-(2-m-tolylethynyl)pyrimidine

Drug Info

[58]

145

5-(2-Methylquinolin-7-yl)-2-phenylbenzonitrile

Drug Info

[23]

146

5-(2-Methylquinolin-7-yl)-2-phenylnicotinonitrile

Drug Info

[23]

147

5-(2-methylquinolin-7-yl)isophthalonitrile

Drug Info

[30]

148

5-(2-methylquinolin-7-yl)nicotinonitrile

Drug Info

[30]

149

5-(3-chlorophenylethynyl)-5-methyl[1,2,4]triazine

Drug Info

[52]

150

5-(phenylethynyl)pyrimidine

Drug Info

[58]

151

5-Biphenyl-4-ylethynyl-pyrimidine

Drug Info

[58]

152

5-Chloro-2-(2-methylquinolin-7-yl)benzonitrile

Drug Info

[23]

153

5-methyl-3-phenylethynyl[1,2,4]triazine

Drug Info

[52]

154

5-[(2-methyl-4-thiazolyl)ethynyl]pyrimidine

Drug Info

[33]

155

6-(4-chlorophenylamino)-N,N-diethylnicotinamide

Drug Info

[61]

156

6-bromo-N-(3-bromophenyl)quinazolin-4-amine

Drug Info

[47]

157

6-bromo-N-(3-chlorophenyl)quinazolin-4-amine

Drug Info

[47]

158

6-bromo-N-(3-fluorophenyl)quinazolin-4-amine

Drug Info

[47]

159

6-bromo-N-m-tolylquinazolin-4-amine

Drug Info

[47]

160

6-chloro-N-(3-chlorophenyl)quinazolin-4-amine

Drug Info

[47]

161

6-fluoro-N-m-tolylquinazolin-4-amine

Drug Info

[47]

162

6-phenylethynyl-nicotinic acid methyl ester

Drug Info

[43]

163

7-(2-methoxyphenyl)-2-methylquinoline

Drug Info

[30]

164

7-(3,5-dimethoxyphenyl)-1,6-naphthyridine

Drug Info

[36]

165

7-(3-(methoxymethyl)phenyl)-2-methylquinoline

Drug Info

[30]

166

7-(3-chlorophenyl)-2-methylquinoline

Drug Info

[30]

167

7-(3-fluoro-5-methylphenyl)-1,6-naphthyridine

Drug Info

[36]

168

7-(3-fluorophenyl)-2-methylquinoline

Drug Info

[30]

169

7-(3-methoxyphenyl)-2-methyl-1,6-naphthyridine

Drug Info

[36]

170

7-(3-methoxyphenyl)-2-methylquinoline

Drug Info

[30]

171

7-(4,6-dimethoxypyrimidin-2-yl)-2-methylquinoline

Drug Info

[51]

172

7-(4,6-dimethylpyrimidin-2-yl)-2-methylquinoline

Drug Info

[51]

173

7-(4-methoxyphenyl)-2-methylquinoline

Drug Info

[30]

174

7-(4-methoxypyrimidin-2-yl)-2-methylquinoline

Drug Info

[51]

175

7-bromo-N-(3-bromophenyl)isoquinolin-1-amine

Drug Info

[47]

176

7-m-tolyl-1,6-naphthyridine

Drug Info

[36]

177

7-methyl-2-m-tolylpyrido[2,3-d]pyrimidine

Drug Info

[37]

178

7-methyl-2-phenylpyrido[2,3-d]pyrimidine

Drug Info

[37]

179

N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[56]

180

N-(1,4-diphenyl-1H-pyrazol-5-yl)benzamide

Drug Info

[56]

181

N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzamide

Drug Info

[56]

182

N-(3-(3-cyanobenzamido)phenyl)-2-methoxybenzamide

Drug Info

[44]

183

N-(3-acetamidophenyl)-3-chlorobenzamide

Drug Info

[44]

184

N-(3-bromophenyl)-6-chloroquinazolin-4-amine

Drug Info

[47]

185

N-(3-bromophenyl)-6-fluoroquinazolin-4-amine

Drug Info

[47]

186

N-(3-chlorophenyl)-3-cyano-5-fluorobenzamide

Drug Info

[54]

187

N-(3-chlorophenyl)-6-fluoroquinazolin-4-amine

Drug Info

[47]

188

N-(3-chlorophenyl)-6-methoxyquinazolin-4-amine

Drug Info

[47]

189

N-(3-chlorophenyl)-6-nitroquinazolin-4-amine

Drug Info

[47]

190

N-(6-methylpyridin-2-yl)-5-phenylpicolinamide

Drug Info

[69]

191

N-(6-methylpyridin-2-yl)-6-phenylnicotinamide

Drug Info

[48]

192

N-(6-methylpyridin-2-yl)biphenyl-3-carboxamide

Drug Info

[48]

193

N-cyclopentyl-6-(2-phenylethynyl)nicotinamide

Drug Info

[70]

194

N-[4-(3-pyridylethynyl)-2-thiazolyl]acetamide

Drug Info

[33]

195

SIB-1757

Drug Info

[53]

196

SIB-1893

Drug Info

[53]

197

[3H]quisqualate

Drug Info

[93]

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: AFQ056

Ligand Info

Structure Description

Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant

PDB:4OO9

Method

X-ray diffraction

Resolution

2.60 Å

Mutation

Yes

[94]

PDB Sequence

SPVQYLRWGD

⁵⁷⁷

PAPIAAVVFA

⁵⁸⁷

CLGLLATLFV

⁵⁹⁷

TVVFIIYRDT

⁶⁰⁷

PVVKSSSREL

⁶¹⁷

CYIILAGICL

⁶²⁷

GYLCTFLIAK

⁶³⁸

PKQIYCYLQR

⁶⁴⁸

IGIGLSPAMS

⁶⁵⁸

YSALVTKTYR

⁶⁶⁸

AARILAMSKK

⁶⁷⁸

NIFEMLRIDE

¹⁰¹¹

GLRLKIYKDT

¹⁰²¹

EGYYTIGIGH

¹⁰³¹

LLTKSPSLNA

¹⁰⁴¹

AKSELDKAIG

¹⁰⁵¹

RNTNGVITKD

¹⁰⁶¹

EAEKLFNQDV

¹⁰⁷¹

DAAVRGILRN

¹⁰⁸¹

AKLKPVYDSL

¹⁰⁹¹

DAVRRAALIN

¹¹⁰¹

MVFQMGETGV

¹¹¹¹

AGFTNSLRML

¹¹²¹

QQKRWDEAAV

¹¹³¹

NLAKSRWYNQ

¹¹⁴¹

TPNRAKRVIT

¹¹⁵¹

TFRTGTWDAY

¹¹⁶¹

KISAAQLVIA

⁶⁹⁷

FILICIQLGI

⁷⁰⁷

IVALFIMEPP

⁷¹⁷

DIMVYLICNT

⁷³⁵

TNLGVVAPLG

⁷⁴⁵

YNGLLILACT

⁷⁵⁵

FYAFKTRNVP

⁷⁶⁵

ANFNEAKYIA

⁷⁷⁵

FTMYTTCIIW

⁷⁸⁵

LAFVPIYFGS

⁷⁹⁵

NYKIITMCFS

⁸⁰⁵

VSLSATVALG

⁸¹⁵

CMFVPKVYII

⁸²⁵

LAKPERN

Residue

Distance (Å)

GLY624

3.547

ILE625

3.781

GLY628

4.118

ILE651

3.584

GLY652

4.620

SER654

3.671

PRO655

3.557

SER658

3.502

TYR659

3.238

VAL740

3.568

PRO743

3.406

LEU744

3.449

Residue

Distance (Å)

ASN747

2.451

ILE751

3.902

ILE784

4.425

TRP785

3.783

PHE788

3.606

MET802

3.939

SER805

2.946

VAL806

3.603

SER809

2.883

ALA810

3.779

ALA813

3.533

Ligand Name: [3H]LY341495

Ligand Info

Structure Description

Thermostabilised full length human mGluR5-5M with orthosteric antagonist, LY341495

PDB:7FD9

Method

Electron microscopy

Resolution

4.00 Å

Mutation

Yes

[95]

PDB Sequence

RRVVAHMPGD

³⁴

IIIGALFSVH

⁴⁴

HQPTVDKVHE

⁵⁴

RKCGAVREQY

⁶⁴

GIQRVEAMLH

⁷⁴

TLERINSDPT

⁸⁴

LLPNITLGCE

⁹⁴

IRDSCWHSAV

¹⁰⁴

ALEQSIEFIR

¹¹⁴

DSLISSKKPI

¹⁴³

VGVIGPGSSS

¹⁵³

VAIQVQNLLQ

¹⁶³

LFNIPQIAYS

¹⁷³

ATSMDLSDKT

¹⁸³

LFKYFMRVVP

¹⁹³

SDAQQARAMV

²⁰³

DIVKRYNWTY

²¹³

VSAVHTEGNY

²²³

GESGMEAFKD

²³³

MSAKEGICIA

²⁴³

HSYKIYSNAG

²⁵³

EQSFDKLLKK

²⁶³

LTSHLPKARV

²⁷³

VACFCEGMTV

²⁸³

RGLLMAMRRL

²⁹³

GLAGEFLLLG

³⁰³

SDGWADRYDV

³¹³

TDGYQREAVG

³²³

GITIKLQSPD

³³³

VKWFDDYYLK

³⁴³

LRPETNLRNP

³⁵³

WFQEFWQHRF

³⁶³

QCRLEGFPQE

³⁷³

NSKYNKTCNS

³⁸³

SLTLKTHHVQ

³⁹³

DSKMGFVINA

⁴⁰³

IYSMAYGLHN

⁴¹³

MQMSLCPGYA

⁴²³

GLCDAMKPID

⁴³³

GRKLLESLMK

⁴⁴³

TAFTGVSGDT

⁴⁵³

ILFDENGDSP

⁴⁶³

GRYEIMNFKE

⁴⁷³

MGKDYFDYIN

⁴⁸³

VGSWDNGELK

⁴⁹³

MDDDEVWSKK

⁵⁰³

SNIIRSVCSE

⁵¹³

PCEKGQIKVI

⁵²³

RKGEVSCCWT

⁵³³

CTPCKENEYV

⁵⁴³

FDEYTCKACQ

⁵⁵³

LGSWPTDDLT

⁵⁶³

GCDLIPVQYL

⁵⁷³

RWGDPEPIAA

⁵⁸³

VVFACLGLLA

⁵⁹³

TLFVTVVFII

⁶⁰³

YRDTPVVKSS

⁶¹³

SRELCYIILA

⁶²³

GICLGYLCTF

⁶³³

CLIAKPKQIY

⁶⁴³

CYLQRIGIGL

⁶⁵³

SPAMSYSALV

⁶⁶³

TKTNRIARIL

⁶⁷³

ACAQLVIAFI

⁶⁹⁹

LICIQLGIIV

⁷⁰⁹

ALFIMEPPDI

⁷¹⁹

MHDYPSIREV

⁷²⁹

YLICNTTNLG

⁷³⁹

VVAPLGYNGL

⁷⁴⁹

LILACTFYAF

⁷⁵⁹

KTRNVPANFN

⁷⁶⁹

EAKYIAFAMY

⁷⁷⁹

TTCIIWLAFV

⁷⁸⁹

PIYFGSNYKA

⁷⁹⁹

ITMCFSVSLS

⁸⁰⁹

ATVLLGCMFV

⁸¹⁹

PKVYIIL

Residue

Distance (Å)

TYR64

2.831

TRP100

3.475

GLY150

3.879

SER151

3.918

SER152

3.253

SER173

2.459

ALA174

3.631

THR175

2.730

Residue

Distance (Å)

SER176

4.161

ASP195

4.094

ASN222

4.192

TYR223

3.527

GLU279

3.787

ASP305

3.691

LYS396

4.199

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). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). 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 Human Pathway Affiliation 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).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

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

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


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.

KEGG Pathway	Pathway ID	Affiliated Target
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Phospholipase D signaling pathway	hsa04072	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Gap junction	hsa04540	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Long-term potentiation	hsa04720	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Retrograde endocannabinoid signaling	hsa04723	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Glutamatergic synapse	hsa04724	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	8	Degree centrality	8.59E-04	Betweenness centrality	9.13E-04
Closeness centrality	2.28E-01	Radiality	1.40E+01	Clustering coefficient	1.43E-01
Neighborhood connectivity	3.20E+01	Topological coefficient	1.37E-01	Eccentricity	12
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 Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 7 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Gap junction

Long-term potentiation

Retrograde endocannabinoid signaling

Glutamatergic synapse

Huntington's disease

Panther Pathway

[+] 4 Panther Pathways

Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway

Metabotropic glutamate receptor group III pathway

Metabotropic glutamate receptor group I pathway

Endogenous cannabinoid signaling

Reactome

[+] 2 Reactome Pathways

G alpha (q) signalling events

Class C/3 (Metabotropic glutamate/pheromone receptors)

WikiPathways

[+] 5 WikiPathways

Hypothetical Network for Drug Addiction

GPCRs, Class C Metabotropic glutamate, pheromone

Gastrin-CREB signalling pathway via PKC and MAPK

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects. Drug Metab Dispos. 2013 Sep;41(9):1626-41.

REF 2

ClinicalTrials.gov (NCT04857359) Dipraglurant (ADX48621) for the Treatment of Patients With Parkinson's Disease Receiving Levodopa-based Therapy. U.S. National Institutes of Health.

REF 3

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7586).

REF 4

ClinicalTrials.gov (NCT01433354) Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label). U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT00820105) ADX10059 Migraine Prevention Study. U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT01750957) A Study of RO4917523 in Pediatric Patients With Fragile X Syndrome. U.S. National Institutes of Health.

REF 7

REF 8

ClinicalTrials.gov (NCT01325740) A Study to Assess the Tolerability of a Single Dose of STX107 in Adults With Fragile X Syndrome. U.S. National Institutes of Health.

REF 9

REF 10

ClinicalTrials.gov (NCT00637221) Open Label Study Investigating Safety and Efficacy of NPL2009 50 mg - 150 mg on Prepulse Inhibition Tests and Continuous Performance Tasks, Adults With Fragile X Syndrome. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT00954538) Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001). U.S. National Institutes of Health.

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040973)

REF 13

ClinicalTrials.gov (NCT01981395) Fenobam on Heat/Capsaicin Induced Hyperalgesia in Healthy Volunteers. U.S. National Institutes of Health.

REF 14

mGlu5 negative allosteric modulators: a patent review (2013 - 2016).Expert Opin Ther Pat. 2017 Jun;27(6):691-706.

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027605)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029648)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015556)

REF 18

Pipeline of Addex Pharma. Addex Pharma. 2009.

REF 19

A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and... Gut. 2009 Sep;58(9):1192-9.

REF 20

Novel treatments of GERD: focus on the lower esophageal sphincter. Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1:103-10.

REF 21

The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl) 2014; 231(6): 1237-1250.

REF 22

Social Communication is an Emerging Target for Pharmacotherapy in Autism Spectrum Disorder - A Review of the Literature on Potential Agents. J Can Acad Child Adolesc Psychiatry. 2014 February; 23(1):20-30.

REF 23

Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic gluta... Bioorg Med Chem. 2010 May 1;18(9):3026-35.

REF 24

Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.

REF 25

REF 26

Clinical pipeline report, company report or official report of Roche.

REF 27

Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agon... J Pharmacol Exp Ther. 2005 Nov;315(2):711-21.

REF 28

Clinical pipeline report, company report or official report of AstraZeneca (2009).

REF 29

Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections. J Neurochem. 2000 Dec;75(6):2590-601.

REF 30

Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4415-8.

REF 31

Dipyridyl amines: potent metabotropic glutamate subtype 5 receptor antagonists. Bioorg Med Chem Lett. 2005 Oct 1;15(19):4350-3.

REF 32

Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate recepto... Bioorg Med Chem. 2009 Aug 1;17(15):5708-15.

REF 33

Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic g... J Med Chem. 2006 Feb 9;49(3):1080-100.

REF 34

Biochemical and electrophysiological studies on (S)-(+)-2-(3'-carboxybicyclo(1.1.1)pentyl)-glycine (CBPG), a novel mGlu5 receptor agonist endowed with mGlu1 receptor antagonist activity. Neuropharmacology. 1999 Jul;38(7):917-26.

REF 35

5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist... Bioorg Med Chem Lett. 2004 Aug 2;14(15):3993-6.

REF 36

Synthesis and SAR comparison of regioisomeric aryl naphthyridines as potent mGlu5 receptor antagonists. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6525-8.

REF 37

Synthesis and SAR of 2-aryl pyrido[2,3-d]pyrimidines as potent mGlu5 receptor antagonists. Bioorg Med Chem Lett. 2007 Oct 1;17(19):5396-9.

REF 38

A new series of pyridinyl-alkynes as antagonists of the metabotropic glutamate receptor 5 (mGluR5). Bioorg Med Chem Lett. 2006 Sep 15;16(18):4792-5.

REF 39

Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1892-7.

REF 40

Structure-activity relationships for the linker in a series of pyridinyl-alkynes that are antagonists of the metabotropic glutamate receptor 5 (mGl... Bioorg Med Chem Lett. 2006 Sep 15;16(18):4788-91.

REF 41

Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a... J Med Chem. 2009 Jul 23;52(14):4103-6.

REF 42

Structure-activity relationship of thiopyrimidines as mGluR5 antagonists. Bioorg Med Chem Lett. 2006 May 1;16(9):2467-9.

REF 43

Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47.

REF 44

Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6502-6.

REF 45

Cyclohexenyl- and dehydropiperidinyl-alkynyl pyridines as potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists. Bioorg Med Chem Lett. 2005 Oct 15;15(20):4589-93.

REF 46

2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology. 1999 Oct;38(10):1493-503.

REF 47

Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6623-6.

REF 48

Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-met... J Med Chem. 2009 Jun 11;52(11):3563-75.

REF 49

A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol Pharmacol. 2003 Sep;64(3):731-40.

REF 50

Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity. J Med Chem. 2004 Sep 9;47(19):4645-8. Letter

REF 51

Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2007 Jun 1;17(11):2987-91.

REF 52

Synthesis and pharmacological evaluation of phenylethynyl[1,2,4]methyltriazines as analogues of 3-methyl-6-(phenylethynyl)pyridine. J Med Chem. 2007 Jul 12;50(14):3388-91.

REF 53

Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3371-5.

REF 54

3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure ... Bioorg Med Chem Lett. 2010 Aug 1;20(15):4390-4.

REF 55

Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo. JMed Chem. 2004 Nov 18;47(24):5825-8.

REF 56

Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat... J Med Chem. 2006 Jun 1;49(11):3332-44.

REF 57

Discovery of novel modulators of metabotropic glutamate receptor subtype-5. Bioorg Med Chem. 2004 Jan 2;12(1):17-21.

REF 58

Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5... Bioorg Med Chem Lett. 2008 Jul 15;18(14):4098-101.

REF 59

A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtyp... Mol Pharmacol. 2005 Dec;68(6):1793-802.

REF 60

Mechanism based neurotoxicity of mGlu5 positive allosteric modulators--development challenges for a promising novel antipsychotic target. Neuropharmacology. 2014 Jul;82:161-73.

REF 61

Piperidyl amides as novel, potent and orally active mGlu5 receptor antagonists with anxiolytic-like activity. Bioorg Med Chem Lett. 2010 Jan 1;20(1):184-8.

REF 62

Dipyridyl amides: potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1197-200.

REF 63

An allosteric modulator to control endogenous G protein-coupled receptors with light. Nat Chem Biol. 2014 Oct;10(10):813-5.

REF 64

A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J Pharmacol Exp Ther. 2004 May;309(2):568-77.

REF 65

Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol. 2011 Jun 1;659(2-3):146-54.

REF 66

CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic glutamate receptor 5 inhibitor. J Pharmacol Exp Ther. 2011 Nov;339(2):474-86.

REF 67

In vitro characterisation of the novel positive allosteric modulators of the mGlu receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat. Neuropharmacology. 2013 Jan;64:224-39.

REF 68

Inhibition of group I metabotropic glutamate receptor responses in vivo in rats by a new generation of carboxyphenylglycine-like amino acid antagon... Neurosci Lett. 2002 Sep 20;330(2):127-30.

REF 69

Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2007 Apr 1;17(7):2074-9.

REF 70

Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3275-8.

REF 71

A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol Pharmacol. 2013 Apr;83(4):835-47.

REF 72

2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl) pyridine: a highly potent, orally active, metabotropic glutamate subtype 5 (mGlu5) receptor antagonist. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5473-6.

REF 73

Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity. Bioorg Med Chem Lett. 2004Nov 15;14(22):5481-4.

REF 74

Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam struc... Bioorg Med Chem Lett. 2007 Mar 1;17(5):1302-6.

REF 75

Design, synthesis, and structure-activity relationships of novel bicyclic azole-amines as negative allosteric modulators of metabotropic glutamate receptor 5. J Med Chem. 2010 Oct 14;53(19):7107-18.

REF 76

Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5). Bioorg Med Chem Lett. 2011 Mar 1;21(5):1402-6.

REF 77

6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4891-9.

REF 78

(3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction. ACS Chem Neurosci. 2011 Aug 17;2(8):471-482.

REF 79

Discovery and structure-activity relationship of 1,3-cyclohexyl amide derivatives as novel mGluR5 negative allosteric modulators. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1398-406.

REF 80

Discovery of (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide, a potent and orally efficacious mGlu5 receptor negative allosteric modulator. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1249-52.

REF 81

Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators. Bioorg Med Chem Lett. 2013 Apr 1;23(7):2134-9.

REF 82

Synthesis and simple 18F-labeling of 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a high affinity radioligand for imaging mo... J Med Chem. 2007 Jul 12;50(14):3256-66.

REF 83

Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function. Mol Pharmacol.2012 Feb;81(2):120-33.

REF 84

Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol. 2010 Dec;78(6):1105-23.

REF 85

Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. ACS Chem Neurosci. 2010 Oct 20;1(10):702-716.

REF 86

Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity. ACS Med Chem Lett. 2010 Nov 11;1(8):433-438.

REF 87

Discovery of 2-(2-benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor (mGlu : from an artificial neural network virtual screen to an in vivo tool compound. ChemMedChem. 2012 Mar 5;7(3):406-14.

REF 88

Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover. Bioorg Med Chem Lett. 2012 Oct 15;22(20):6481-5.

REF 89

Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry. 2013 Mar 15;73(6):501-9.

REF 90

Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction. ACS Chem Neurosci. 2013Aug 21;4(8):1217-28.

REF 91

[3H]Methoxymethyl-3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain: in vitro and in vivo characterization. J Pharmacol Exp Ther. 2002 Dec;303(3):1044-51.

REF 92

[3H]-methoxymethyl-MTEP and [3H]-methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett. 2003 Feb 10;13(3):351-4.

REF 93

Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)... J Med Chem. 1998 Mar 12;41(6):930-9.

REF 94

Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature. 2014 Jul 31;511(7511):557-62.

REF 95

Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations. Cell Rep. 2021 Aug 31;36(9):109648.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU