Therapeutic Targets Database
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TTD Target ID: TTDC00100

Target Information
NameMetabotropic glutamate receptor 5    
Type of targetClinical trial target    
Synonyms5b    
Glutamate receptor mGLU5    
mGluR5    
DiseaseAnalgesics
[ICD9: 338   ICD10: R52]
[1][2]
Anxiety Disorders
[ICD9: 300   ICD10: F40-F42]
[3][4][2]
Convulsions
[ICD9: 780.3   ICD10: R56.0]
[2]
Depression
[ICD9: 311   ICD10: F32]
[5]
Drug dependence
[ICD9: 303-304   ICD10: F10.2-F19.2]
[2]
Gastroesophageal Reflux Disease (GERD)
[ICD9: 530   ICD10: K21]
[3][4]
Inflammatory pain
[ICD9: 338,780   ICD10: R52, G89]
[1][2]
Migraine and Cluster Headaches
[ICD9: 339.00, 339.01, 339.02, 346   ICD10: G43, G44.0]
[3][4]
Neuronal injury[2]
Parkinson's disease
[ICD9: 332   ICD10: F02.3, G20]
[2]
Drug(s)AZD2066Phase IIMajor Depressive Disorder; GERD; chronic neuropathic pain[6]
RG7090Phase IIFragile X syndrome (see also depression)
RG7090Phase IIMajor depressive disorder (see also developmental)
RG7090Phase IITreatment-resistant depression
STX107Phase IIFragile X syndrome
AFQ056Phase I/IIFragile X syndrome (lead indication), L-dopa-induced dyskinesia in Parkinson's disease
AZD2516Phase I/IIReflux; Chronic neuropathic pain[6]
ADX-48621Phase IDepression[7]
ADX10059Terminated in Phase IIaAnxiety Disorders[3][4]
ADX10059Terminated in Phase IIaMigraine and Cluster Headaches, Gastroesophageal Reflux Disease[3][4]
McN3377Discontinued in Phase IIAnxiety[8]
LY467711PreclinicalNeuropathic pain and Migraine[8]
LY525327PreclinicalNeuropathic pain and Migraine[8]
MGluRIII agonist and mGlu5 antagonistPreclinicalParkinsoní»s Disease[9]
BioChemical ClassG-protein coupled receptor (metabotropic glutamate family)    
PathwayCalcium signaling pathway
Gap junction
Huntington's disease
Long-term depression
Long-term potentiation
Neuroactive ligand-receptor interaction
UniProt IDP41594
PDB Structure3LMK.    
FunctionReceptor for glutamate. The activity of this receptor is mediated by a g-protein that activates a phosphatidylinositol- calcium second messenger system and generates a calcium-activated chloride current.    
SequenceMVLLLILSVLLLKEDVRGSAQSSERRVVAHMPGDIIIGALFSVHHQPTVDKVHERKCGAV REQYGIQRVEAMLHTLERINSDPTLLPNITLGCEIRDSCWHSAVALEQSIEFIRDSLISS EEEEGLVRCVDGSSSSFRSKKPIVGVIGPGSSSVAIQVQNLLQLFNIPQIAYSATSMDLS DKTLFKYFMRVVPSDAQQARAMVDIVKRYNWTYVSAVHTEGNYGESGMEAFKDMSAKEGI CIAHSYKIYSNAGEQSFDKLLKKLTSHLPKARVVACFCEGMTVRGLLMAMRRLGLAGEFL LLGSDGWADRYDVTDGYQREAVGGITIKLQSPDVKWFDDYYLKLRPETNHRNPWFQEFWQ HRFQCRLEGFPQENSKYNKTCNSSLTLKTHHVQDSKMGFVINAIYSMAYGLHNMQMSLCP GYAGLCDAMKPIDGRKLLESLMKTNFTGVSGDTILFDENGDSPGRYEIMNFKEMGKDYFD YINVGSWDNGELKMDDDEVWSKKSNIIRSVCSEPCEKGQIKVIRKGEVSCCWTCTPCKEN EYVFDEYTCKACQLGSWPTDDLTGCDLIPVQYLRWGDPEPIAAVVFACLGLLATLFVTVV FIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAMSYS ALVTKTNRIARILAGSKKKICTKKPRFMSACAQLVIAFILICIQLGIIVALFIMEPPDIM HDYPSIREVYLICNTTNLGVVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYT TCIIWLAFVPIYFGSNYKIITMCFSVSLSATVALGCMFVPKVYIILAKPERNVRSAFTTS TVVRMHVGDGKSSSAASRSSSLVNLWKRRGSSGETLRYKDRRLAQHKSEIECFTPKGSMG NGGRATMSSSNGKSVTWAQNEKSSRGQHLWQRLSIHINKKENPNQTAVIKPFPKSTESRG LGAGAGAGGSAGGVGATGGAGCAGAGPGGPESPDAGPKALYDVAEAEEHFPAPARPRSPS PISTLSHRAGSASRTDDDVPSLHSEPVARSSSSQGSLMEQISSVVTRFTANISELNSMML STAAPSPGVGAPLCSSYLIPKEIQLPTTMTTFAEIQPLPAIEVTGGAQPAAGAQAAGDAA RESPAAGPEAAAAKPDLEELVALTPPSPFRDSVDSGSTTPNSPVSESALCIPSSPKYDTL IIRDYTQSSSSL
Related US Patent6,660,753
Target ValidationClick to Find Target Validation Information.    
InhibitorGLUTAMATE[10]
N- (1,3-diphenyl-1H-pyrazol-5-yl)benzamide[11]
N- (1,4-diphenyl-1H-pyrazol-5-yl)benzamide[11]
N- (2-phenylimidazo[1,2-a]pyridin-3-yl)benzamide[11]
N- (3-[12]
N- (3-acetamidophenyl)-3-chlorobenzamide[12]
N- (3-bromophenyl)-6-chloroquinazolin-4-amine[13]
N- (3-bromophenyl)-6-fluoroquinazolin-4-amine[13]
N- (3-chlorophenyl)-3-cyano-5-fluorobenzamide[14]
N- (3-chlorophenyl)-6-fluoroquinazolin-4-amine[13]
N- (3-chlorophenyl)-6-methoxyquinazolin-4-amine[13]
N- (3-chlorophenyl)-6-nitroquinazolin-4-amine[13]
N- (6-methylpyridin-2-yl)-5-phenylpicolinamide[15]
N- (6-methylpyridin-2-yl)-6-phenylnicotinamide[16]
N- (6-methylpyridin-2-yl)biphenyl-3-carboxamide[16]
N-[4- (3-pyridylethynyl)-2-thiazolyl]acetamide[17]
N-cyclopentyl-6- (2-phenylethynyl)nicotinamide[18]
QUISQUALATE[19]
SIB-1757[20]
SIB-1893[20]
AntagonistAZD2066[6]
AZD2516[6]
LY467711[8]
LY525327[8]
MGluRIII agonist and mGlu5 antagonist[9]
ModulatorADX-48621[7]
ADX10059[3][4]
McN3377[8]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Peripheral metabotropic glutamate receptors: fight the pain where it hurts. Trends Neurosci. 2001 Oct;24(10):550-2. To Reference
Ref 2Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol. 2002 Feb;2(1):43-9. To Reference
Ref 3Gut. 2009 Sep;58(9):1192-9. Epub 2009 May 20.A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and symptoms in gastro-oesophageal reflux disease. To Reference
Ref 4Novel treatments of GERD: focus on the lower esophageal sphincter. Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1:103-10. To Reference
Ref 5CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. To Reference
Ref 6AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 7Pipeline of Addex Pharma. Addex Pharma. 2009 To Reference
Ref 8Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. To Reference
Ref 9Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. To Reference
Ref 10J Med Chem. 2007 Sep 20;50(19):4630-41. Epub 2007 Aug 29.Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs. To Reference
Ref 11J Med Chem. 2006 Jun 1;49(11):3332-44.Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes. To Reference
Ref 12Bioorg Med Chem Lett. 2009 Dec 1;19(23):6502-6. Epub 2009 Oct 28.Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS. To Reference
Ref 13Bioorg Med Chem Lett. 2009 Dec 1;19(23):6623-6. Epub 2009 Oct 9.Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5. To Reference
Ref 14Bioorg Med Chem Lett. 2010 Aug 1;20(15):4390-4. Epub 2010 Jun 15.3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats. To Reference
Ref 15Bioorg Med Chem Lett. 2007 Apr 1;17(7):2074-9. Epub 2007 Jan 4.Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists. To Reference
Ref 16J Med Chem. 2009 Jun 11;52(11):3563-75.Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists. To Reference
Ref 17J Med Chem. 2006 Feb 9;49(3):1080-100.Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications. To Reference
Ref 18Bioorg Med Chem Lett. 2009 Jun 15;19(12):3275-8. Epub 2009 Apr 24.Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator. To Reference
Ref 19J Med Chem. 1998 Mar 12;41(6):930-9.Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid. To Reference
Ref 20Bioorg Med Chem Lett. 2006 Jul 1;16(13):3371-5. Epub 2006 May 5.Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists. To Reference



 

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