Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVBPDM)

• DTT Name: Metabotropic glutamate receptor 1 (mGluR1)
• Synonyms: mGLUR1; Glutamate receptor mGLU1; GPRC1A
• Gene Name: GRM1
• DTT Type: Discontinued target; [1]
• Related Disease:
  Alzheimer disease [ICD-11: 8A20]
  Schizophrenia [ICD-11: 6A20]
  General pain disorder [ICD-11: 8E43]
  Cerebral ischaemia [ICD-11: 8B1Z]
  Pain [ICD-11: MG30-MG3Z]
  Dissociative neurological symptom disorder [ICD-11: 6B60]
• BioChemical Class: GPCR glutamate
• UniProt ID: GRM1_HUMAN
• TTD ID: T27137
• Sequence:
  MVGLLLFFFPAIFLEVSLLPRSPGRKVLLAGASSQRSVARMDGDVIIGALFSVHHQPPAE
  KVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSI
  EFIRDSLISIRDEKDGINRCLPDGQSLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDI
  PQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESG
  MDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVRGLL
  SAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLD
  TNTRNPWFPEFWQHRFQCRLPGHLLENPNFKRICTGNESLEENYVQDSKMGFVINAIYAM
  AHGLQNMHHALCPGHVGLCDAMKPIDGSKLLDFLIKSSFIGVSGEEVWFDEKGDAPGRYD
  IMNLQYTEANRYDYVHVGTWHEGVLNIDDYKIQMNKSGVVRSVCSEPCLKGQIKVIRKGE
  VSCCWICTACKENEYVQDEFTCKACDLGWWPNADLTGCEPIPVRYLEWSNIESIIAIAFS
  CLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQ
  RLLVGLSSAMCYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTL
  VVTLIIMEPPMPILSYPSIKEVYLICNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVPAN
  FNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMFTPKMYIIIA
  KPERNVRSAFTTSDVVRMHVGDGKLPCRSNTFLNIFRRKKAGAGNANSNGKSVSWSEPGG
  GQVPKGQHMWHRLSVHVKTNETACNQTAVIKPLTKSYQGSGKSLTFSDTSTKTLYNVEEE
  EDAQPIRFSPPGSPSMVVHRRVPSAATTPPLPSHLTAEETPLFLAEPALPKGLPPPLQQQ
  QQPPPQQKSLMDQLQGVVSNFSTAIPDFHAVLAGPGGPGNGLRSLYPPPPPPQHLQMLPL
  QLSTFGEELVSPPADDDDDSERFKLLQEYVYEHEREGNTEEDELEEEEEDLQAASKLTPD
  DSPALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVSYASVILRDYKQSSSTL
• Function: 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. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum. G-protein coupled receptor for glutamate.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  FoxO signaling pathway (hsa04068)
  Neuroactive ligand-receptor interaction (hsa04080)
  Gap junction (hsa04540)
  Long-term potentiation (hsa04720)
  Retrograde endocannabinoid signaling (hsa04723)
  Glutamatergic synapse (hsa04724)
  Long-term depression (hsa04730)
  Estrogen signaling pathway (hsa04915)
• Reactome Pathway:
  Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DTT

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-1913539	DMXEU14	Alzheimer disease	8A20	Discontinued in Phase 3	[2], [3]
AZD8529	DMEQ2N1	Schizophrenia	6A20	Discontinued in Phase 2	[4]
AZD-9272	DMYSBN3	Neuropathic pain	8E43.0	Discontinued in Phase 1	[5]
LY-367385	DM98POQ	Neurological disorder	6B60	Terminated	[7]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-841720	DMSO8IE	Pain	MG30-MG3Z	Preclinical	[1]
NPS-2390	DMMRY0Z	Cerebrovascular ischaemia	8B1Z	Preclinical	[6]

84 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[8], [9]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[10]
(3,4-dimethylphenyl)(4-phenoxyphenyl)methanone	DMAF43E	Discovery agent	N.A.	Investigative	[11]
(E)-1-Adamantan-1-yl-3-quinolin-3-yl-propenone	DMQ9TWD	Discovery agent	N.A.	Investigative	[11]
(E)-4,4-Dimethyl-1-quinolin-3-yl-pent-1-en-3-one	DMJGAFV	Discovery agent	N.A.	Investigative	[11]
(S)-(+)-CBPG	DMPDOY8	Discovery agent	N.A.	Investigative	[12]
(S)-3HPG	DMQ0FVJ	Discovery agent	N.A.	Investigative	[10]
(S)-4C3HPG	DMQK4I2	Discovery agent	N.A.	Investigative	[10]
(S)-4CPG	DMZ9UIL	Discovery agent	N.A.	Investigative	[8]
(S)-TBPG	DM68XFZ	Discovery agent	N.A.	Investigative	[13]
2-methyl-6-(phenylethynyl)pyridine	DMVQK4Y	Discovery agent	N.A.	Investigative	[14]
3,5-DHPG	DMFEQ6S	Discovery agent	N.A.	Investigative	[8]
3,5-dimethyl PPP	DM3E98I	Discovery agent	N.A.	Investigative	[15]
3-MATIDA	DMRMF13	Discovery agent	N.A.	Investigative	[16]
4-(cyclohexyloxy)quinazoline	DMCDZ7E	Discovery agent	N.A.	Investigative	[17]
6-bromo-N-(3-chlorophenyl)quinazolin-4-amine	DM0A3DB	Discovery agent	N.A.	Investigative	[18]
A-794278	DM6BRTF	Discovery agent	N.A.	Investigative	[19]
A-794282	DMU965M	Discovery agent	N.A.	Investigative	[19]
A-850002	DMJCPSD	Discovery agent	N.A.	Investigative	[19]
AIDA	DM3LCDK	Discovery agent	N.A.	Investigative	[8]
BAY 367620	DMVP74I	Discovery agent	N.A.	Investigative	[20]
CFMMC	DMN8B1S	Discovery agent	N.A.	Investigative	[21]
CFMTI	DM9HMP4	Discovery agent	N.A.	Investigative	[22]
CPCCOEt	DMI4WVE	Discovery agent	N.A.	Investigative	[8]
DM-PPP	DMUGPD1	Discovery agent	N.A.	Investigative	[15]
FPTQ	DMR2NBK	Discovery agent	N.A.	Investigative	[23]
FTIDC	DM65VLB	Discovery agent	N.A.	Investigative	[24]
ibotenate	DM8RZE0	Discovery agent	N.A.	Investigative	[10]
JNJ-16567083	DMXNFU5	Discovery agent	N.A.	Investigative	[25]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[10]
LY-3390334	DMUXFZQ	Discovery agent	N.A.	Investigative	[26]
LY456066	DM86Y1V	Discovery agent	N.A.	Investigative	[21]
LY456236	DMROFX8	Discovery agent	N.A.	Investigative	[27]
MK-5435	DMU8VRB	Discovery agent	N.A.	Investigative	[28]
N-(2,3-dihydro-1H-inden-2-yl)isoquinolin-1-amine	DMTLPDZ	Discovery agent	N.A.	Investigative	[17]
N-(2,3-dihydro-1H-inden-2-yl)quinazolin-4-amine	DMJ6LI8	Discovery agent	N.A.	Investigative	[17]
N-(2-methyl-2-phenylpropyl)pyrazine-2-carboxamide	DMXRSM1	Discovery agent	N.A.	Investigative	[29]
N-(2-phenylpropyl)quinoxaline-2-carboxamide	DMA1LRF	Discovery agent	N.A.	Investigative	[29]
N-(3-bromophenyl)-6-chloroquinazolin-4-amine	DMEWQCN	Discovery agent	N.A.	Investigative	[18]
N-(3-bromophenyl)-6-fluoroquinazolin-4-amine	DMRIK7P	Discovery agent	N.A.	Investigative	[18]
N-cyclohexylquinazolin-4-amine	DMJ0T3W	Discovery agent	N.A.	Investigative	[17]
N-cyclohexylquinolin-4-amine	DMJY2PA	Discovery agent	N.A.	Investigative	[17]
N-phenethylquinoxaline-2-carboxamide	DM1ZPGY	Discovery agent	N.A.	Investigative	[29]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[27]
PMID12470711C3	DM1ISJU	Discovery agent	N.A.	Investigative	[15]
PMID16099654C3a	DMIRSWL	Discovery agent	N.A.	Investigative	[30]
PMID16099654C4b	DMV8UK1	Discovery agent	N.A.	Investigative	[30]
PMID17064898C29	DMITDEB	Discovery agent	N.A.	Investigative	[29]
PMID17276684C22	DMWNYBV	Discovery agent	N.A.	Investigative	[31]
PMID17532216C2f	DMX3CYG	Discovery agent	N.A.	Investigative	[32]
PMID17929793C11c	DMDVW4K	Discovery agent	N.A.	Investigative	[33]
PMID17929793C23c	DMIG308	Discovery agent	N.A.	Investigative	[33]
PMID17929793C23e	DMOB07W	Discovery agent	N.A.	Investigative	[33]
PMID17929793C23h	DM83Z6M	Discovery agent	N.A.	Investigative	[33]
PMID17929793C23i	DM07TVS	Discovery agent	N.A.	Investigative	[33]
PMID19289283C22	DMJRLB5	Discovery agent	N.A.	Investigative	[17]
PMID19289283C32	DMSKGEJ	Discovery agent	N.A.	Investigative	[17]
PMID19433355C11q	DMPXEIQ	Discovery agent	N.A.	Investigative	[34]
PMID19433355C11s	DMBU0XJ	Discovery agent	N.A.	Investigative	[34]
PMID20346665C24	DMLKFTE	Discovery agent	N.A.	Investigative	[35]
PMID20346665C27	DMDKW6G	Discovery agent	N.A.	Investigative	[35]
PMID22266036C12e	DM4NRG5	Discovery agent	N.A.	Investigative	[36]
PMID22266036C9a	DMFQHVL	Discovery agent	N.A.	Investigative	[36]
PMID23084894C10i	DMURP5Y	Discovery agent	N.A.	Investigative	[37]
PMID23084894C9n	DM4ATLM	Discovery agent	N.A.	Investigative	[37]
Pyrazine-2-carboxylic acid adamantan-1-ylamide	DMIZB81	Discovery agent	N.A.	Investigative	[6]
Quinoline-2-carboxylic acid adamantan-1-ylamide	DMDY3I2	Discovery agent	N.A.	Investigative	[6]
Quinoline-3-carboxylic acid adamantan-1-ylamide	DM9BIVL	Discovery agent	N.A.	Investigative	[6]
R214127	DMX80BL	Discovery agent	N.A.	Investigative	[8]
Ro01-6128	DM0AC84	Discovery agent	N.A.	Investigative	[38]
Ro0711401	DMZLUAK	Discovery agent	N.A.	Investigative	[39]
Ro67-4853	DMD93NP	Discovery agent	N.A.	Investigative	[38]
Ro67-7476	DMI95DP	Discovery agent	N.A.	Investigative	[38]
VU-71	DMHX1KJ	Discovery agent	N.A.	Investigative	[30]
VU0080241	DMUMOV1	Discovery agent	N.A.	Investigative	[40]
VU0469650	DM1H5DL	Discovery agent	N.A.	Investigative	[41]
YM-202074	DM3IOLR	Discovery agent	N.A.	Investigative	[42]
YM298198	DMUYDXT	Discovery agent	N.A.	Investigative	[43]
[11C]MMTP	DMQRSP7	Discovery agent	N.A.	Investigative	[44]
[18F]FITM	DM4VQNE	Discovery agent	N.A.	Investigative	[45]
[18F]FPIT	DMRQ6XD	Discovery agent	N.A.	Investigative	[46]
[18F]MK-1312	DMQ6AR5	Discovery agent	N.A.	Investigative	[28]
[3H]EM-TBPC	DMM1KBW	Discovery agent	N.A.	Investigative	[47]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[47], [48]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	2.31E-01	-0.05	-0.2
Schizophrenia	6A20	Superior temporal cortex	2.46E-02	0.11	0.74

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