Target Information

Target General Infomation
Target ID
T09572
Former ID
TTDC00133
Target Name
Melanin-concentrating hormone receptor 1
Gene Name
MCHR1
Synonyms
G protein coupled receptor 24; MCH receptor1; MCH(1) receptor; MCH-1R; MCH-R1; MCH1R; MCHR; MCHR-1; Melanin-concentrating hormone receptor subtype 1; SLC-1; Somatostatinreceptor-like protein; MCHR1
Target Type
Clinical Trial
Disease Obesity [ICD9: 278; ICD10: E66]
Obesity; Anxiety; Depression [ICD9: 278, 300, 311; ICD10: E66, F32, F40-F42]
Function
Receptor formelanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
BioChemical Class
GPCR rhodopsin
Target Validation
T09572
UniProt ID
Q99705
Sequence
MSVGAMKKGVGRAVGLGGGSGCQATEEDPLPNCGACAPGQGGRRWRLPQPAWVEGSSARL
WEQATGTGWMDLEASLLPTGPNASNTSDGPDNLTSAGSPPRTGSISYINIIMPSVFGTIC
LLGIIGNSTVIFAVVKKSKLHWCNNVPDIFIINLSVVDLLFLLGMPFMIHQLMGNGVWHF
GETMCTLITAMDANSQFTSTYILTAMAIDRYLATVHPISSTKFRKPSVATLVICLLWALS
FISITPVWLYARLIPFPGGAVGCGIRLPNPDTDLYWFTLYQFFLAFALPFVVITAAYVRI
LQRMTSSVAPASQRSIRLRTKRVTRTAIAICLVFFVCWAPYYVLQLTQLSISRPTLTFVY
LYNAAISLGYANSCLNPFVYIVLCETFRKRLVLSVKPAAQGQLRAVSNAQTADEERTESK
GT
Drugs and Mode of Action
Drug(s) AZD1979 Drug Info Phase 1 Obesity [524658]
BMS-830216 Drug Info Phase 1 Obesity [550384]
MCH antagonist Drug Info Preclinical Obesity [536122]
SNAP-7941 Drug Info Preclinical Obesity; Anxiety; Depression [536122], [538804]
T-226293 Drug Info Preclinical Obesity [536122]
T-226296 Drug Info Preclinical Obesity [536122], [538805]
AMG 076 Drug Info Discontinued in Phase 1 Obesity [547852]
NGD-4715 Drug Info Discontinued in Phase 1 Obesity [548402]
A-798 Drug Info Terminated Obesity [548089]
ALB-127158(a) Drug Info Terminated Obesity [550255]
Inhibitor 2-phenyl-N,N-bis(o-tolylthiomethyl)ethanamine Drug Info [529257]
8-(1,2-Dimethyl-propoxy)-quinolin-2-ylamine Drug Info [527194]
8-(1,3,3-Trimethyl-butoxy)-quinolin-2-ylamine Drug Info [527195]
8-(1-Ethyl-propoxy)-quinolin-2-ylamine Drug Info [527194]
8-(1-Methyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Cyclopropyl-ethoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Ethoxy-1-methyl-ethoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Ethyl-1-methyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Methoxy-1-methyl-ethoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Methyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(2-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info [527194]
8-(3,3,3-trifluoropropoxy)quinolin-2-amine Drug Info [527194]
8-(3,3-Dimethyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(3-Methoxy-3-methyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(3-Methyl-butoxy)-quinolin-2-ylamine Drug Info [527194]
8-(3-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info [527194]
8-(3-Methyl-cyclopentyloxy)-quinolin-2-ylamine Drug Info [527194]
8-(4-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info [527194]
8-Butoxy-quinolin-2-ylamine Drug Info [527194]
8-Cyclobutylmethoxy-quinolin-2-ylamine Drug Info [527194]
8-Cycloheptyloxy-quinolin-2-ylamine Drug Info [527194]
8-Cyclohexyloxy-quinolin-2-ylamine Drug Info [527194]
8-Cyclopentylmethoxy-quinolin-2-ylamine Drug Info [527194]
8-Hexyloxy-quinolin-2-ylamine Drug Info [527194]
8-Isopropoxy-quinolin-2-ylamine Drug Info [527194]
8-Methoxy-quinolin-2-ylamine Drug Info [527194]
8-Pentyloxy-quinolin-2-ylamine Drug Info [527194]
8-Propoxy-quinolin-2-ylamine Drug Info [527194]
8-sec-Butoxy-quinolin-2-ylamine Drug Info [527194]
A-224940 Drug Info [527196]
ADS-102891 Drug Info [528581]
ADS-103168 Drug Info [528581]
ADS-103214 Drug Info [528581]
ADS-103253 Drug Info [528581]
ADS-103254 Drug Info [528581]
ADS-103274 Drug Info [528581]
ADS-103293 Drug Info [528581]
ADS-103294 Drug Info [528581]
ADS-103316 Drug Info [528581]
AR-129330 Drug Info [527629]
GNF-PF-1550 Drug Info [527713]
GNF-PF-2322 Drug Info [527713]
N,N-bis(tosylmethyl)hexan-1-amine Drug Info [529257]
N-(1-benzylpiperidin-4-yl)-3,5-dimethoxybenzamide Drug Info [528347]
N-(4-amino-2-propylquinolin-6-yl)cinnamamide Drug Info [528381]
Phenyl-N,N-bis(tosylmethyl)methanamine Drug Info [529257]
Antagonist 4-arylphthalazin-1(2H)-3,4-Di-F Drug Info [531725]
7-fluorochromone-2-carboxamide Drug Info [528492]
A-798 Drug Info [532063]
ALB-127158(a) Drug Info [550255]
AMG 076 Drug Info [536531]
ATC0065 Drug Info [527402]
AZ13483342 Drug Info [528866]
BMS-830216 Drug Info [550384]
compound (R)-10h Drug Info [531871]
compound 17 Drug Info [528543]
compound 4b Drug Info [530316]
GW803430 Drug Info [528336]
MCH antagonist Drug Info [536122]
MCHR1 antagonists Drug Info [543715]
NGD-4715 Drug Info [550543]
pyrrolidine MCHR1 antagonist 1 Drug Info [531400]
SB-568849 Drug Info [528310]
SNAP-7941 Drug Info [536122]
T-226293 Drug Info [536122]
T-226296 Drug Info [536122]
tetralin_urea analogue (7o) Drug Info [528636]
TPI-1361-17 Drug Info [543715]
[3H]SNAP-7941 Drug Info [526378]
Modulator AZD1979 Drug Info [550345]
Agonist C3 Drug Info [526145]
melanin-concentrating hormone Drug Info [526070]
Modulator (allosteric modulator) MQ1 Drug Info [532720]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Reactome Peptide ligand-binding receptors
G alpha (q) signalling events
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
GPCR ligand binding
GPCR downstream signaling
References
Ref 524658ClinicalTrials.gov (NCT02072993) A First Time in Man Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD1979 in Healthy Males. U.S. National Institutes of Health.
Ref 536122Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
Ref 538804(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: 1313).
Ref 538805(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: 1314).
Ref 547852Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019931)
Ref 548089Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021828)
Ref 548402Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025311)
Ref 550255Clinical pipeline report, company report or official report of Albany Molecular Research (2011).
Ref 5503842011 Pipeline of Bristol-Myers Squibb.
Ref 526070[125I]-S36057: a new and highly potent radioligand for the melanin-concentrating hormone receptor. Br J Pharmacol. 2001 Jun;133(3):371-8.
Ref 526145SLC-1 receptor mediates effect of melanin-concentrating hormone on feeding behavior in rat: a structure-activity study. J Pharmacol Exp Ther. 2001 Oct;299(1):137-46.
Ref 526378Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med. 2002 Aug;8(8):825-30. Epub 2002 Jul 15.
Ref 527194Bioorg Med Chem Lett. 2004 Oct 4;14(19):4873-7.Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 1.
Ref 527195Bioorg Med Chem Lett. 2004 Oct 4;14(19):4879-82.Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 2.
Ref 527196Bioorg Med Chem Lett. 2004 Oct 4;14(19):4883-6.Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 3.
Ref 527402Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. J Pharmacol Exp Ther. 2005 May;313(2):831-9. Epub 2005 Jan 26.
Ref 527629Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6.Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1.
Ref 527713J Med Chem. 2005 Sep 8;48(18):5684-97.6-Acylamino-2-aminoquinolines as potent melanin-concentrating hormone 1 receptor antagonists. Identification, structure-activity relationship, and investigation of binding mode.
Ref 528310Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4872-8. Epub 2006 Jul 12.
Ref 528336The discovery and optimization of pyrimidinone-containing MCH R1 antagonists. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4723-7. Epub 2006 Jul 25.
Ref 528347Bioorg Med Chem Lett. 2006 Oct 15;16(20):5445-50. Epub 2006 Aug 1.Identification of substituted 4-aminopiperidines and 3-aminopyrrolidines as potent MCH-R1 antagonists for the treatment of obesity.
Ref 528381Bioorg Med Chem Lett. 2006 Oct 15;16(20):5275-9. Epub 2006 Aug 17.4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists.
Ref 528492Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: assessment of potency, efficacy, and cardiovascular safety. J Med Chem. 2006 Nov 2;49(22):6569-84.
Ref 5285436-(4-chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-based melanin-concentrating hormone receptor 1 antagonist. J Med Chem. 2006 Nov 30;49(24):7108-18.
Ref 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.
Ref 528636Discovery of tetralin ureas as potent melanin concentrating hormone 1 receptor antagonists. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1718-21. Epub 2006 Dec 24.
Ref 528866Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists. Bioorg Med Chem Lett. 2007 Aug 1;17(15):4232-41. Epub 2007 May 17.
Ref 529257J Med Chem. 2008 Feb 14;51(3):581-8. Epub 2008 Jan 17.Discovery of novel chemotypes to a G-protein-coupled receptor through ligand-steered homology modeling and structure-based virtual screening.
Ref 530316Bioorg Med Chem Lett. 2009 Sep 15;19(18):5339-45. Epub 2009 Aug 6.Discovery of novel diarylketoxime derivatives as selective and orally active melanin-concentrating hormone 1 receptor antagonists.
Ref 531400Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2460-7.
Ref 5317254-arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1). Bioorg Med Chem Lett. 2012 Jan 1;22(1):427-30.
Ref 531871Synthesis, structure-activity relationship, and pharmacological studies of novel melanin-concentrating hormone receptor 1 antagonists 3-aminomethylquinolines: reducing human ether-a-go-go-related gene (hERG) associated liabilities. J Med Chem. 2012 May 10;55(9):4336-51.
Ref 532063Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function. Endocrinology. 2012 Dec;153(12):6145-54.
Ref 532720The MCH(1) receptor, an anti-obesity target, is allosterically inhibited by 8-methylquinoline derivatives possessing subnanomolar binding and long residence times. Br J Pharmacol. 2014 Mar;171(5):1287-98.
Ref 536122Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
Ref 536531Stereoselective synthesis of a MCHr1 antagonist. J Org Chem. 2007 Dec 7;72(25):9648-55. Epub 2007 Nov 13.
Ref 543715(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. (Target id: 280).
Ref 550255Clinical pipeline report, company report or official report of Albany Molecular Research (2011).
Ref 550345Phase I clinical trial of AZD1979 for treating obesity. AstraZeneca plc
Ref 5503842011 Pipeline of Bristol-Myers Squibb.
Ref 550543CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.

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