Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTX4RTB)

• DTT Name: Melanin-concentrating hormone receptor 1 (MCHR1)
• Synonyms: Somatostatinreceptor-like protein; Somatostatin receptor-like protein; SLC1; SLC-1; Melanin-concentrating hormone receptor subtype 1; MCHR-1; MCHR; MCH1R; MCH-R1; MCH-1R; MCH(1) receptor; MCH receptor1; MCH receptor 1; GPR24; G-protein coupled receptor 24; G protein coupled receptor 24
• Gene Name: MCHR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: MCHR1_HUMAN
• TTD ID: T09572
• Sequence:
  MSVGAMKKGVGRAVGLGGGSGCQATEEDPLPNCGACAPGQGGRRWRLPQPAWVEGSSARL
  WEQATGTGWMDLEASLLPTGPNASNTSDGPDNLTSAGSPPRTGSISYINIIMPSVFGTIC
  LLGIIGNSTVIFAVVKKSKLHWCNNVPDIFIINLSVVDLLFLLGMPFMIHQLMGNGVWHF
  GETMCTLITAMDANSQFTSTYILTAMAIDRYLATVHPISSTKFRKPSVATLVICLLWALS
  FISITPVWLYARLIPFPGGAVGCGIRLPNPDTDLYWFTLYQFFLAFALPFVVITAAYVRI
  LQRMTSSVAPASQRSIRLRTKRVTRTAIAICLVFFVCWAPYYVLQLTQLSISRPTLTFVY
  LYNAAISLGYANSCLNPFVYIVLCETFRKRLVLSVKPAAQGQLRAVSNAQTADEERTESK
  GT
• Function: Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD1979	DMQ1OX4	Obesity	5B81	Phase 1	[1]
BMS-830216	DMCW71N	Obesity	5B81	Phase 1	[2]

50 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25522065-Compound-10	DMRJ30G	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-11	DM410Z6	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-12	DMVKO9C	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-13	DM92HZG	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-14	DMGZER5	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-15	DMZMQFW	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-16	DMAN3BT	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-17	DM7X6HR	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-18	DMTPJI8	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-19	DMP4VYQ	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-2	DM3I6OF	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-20	DMG5J9Z	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-21	DMRZMH5	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-22	DM1N5UH	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-23	DMHSGPU	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-24	DM9MLQ6	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-25	DMUM3YW	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-26	DMY07NA	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-27	DMXN4KB	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-28	DMB93QU	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-29	DMBNAK9	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-3	DM54DXT	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-30	DMMOV67	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-31	DMEMBOW	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-32	DM5H3YA	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-33	DMYMJIW	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-34	DMZDIRQ	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-35	DM1JAFV	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-36	DMNISGE	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-37	DMH3CK0	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-38	DMQLBAJ	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-39	DM5YMQH	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-4	DM84U7F	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-40	DMCIQ01	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-41	DMWALOT	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-42	DMAUO6C	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-43	DMS1FKC	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-44	DMJKOFB	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-45	DMONJLT	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-46	DMBH97R	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-47	DMXRI5J	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-48	DMHI4L6	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-49	DMNI03Z	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-5	DMA8G6B	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-50	DMBWA0V	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-51	DMEU48I	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-6	DMU1PEZ	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-7	DMYZMX6	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-8	DMJMCKD	N. A.	N. A.	Patented	[3]
PMID25522065-Compound-9	DMAMRPW	N. A.	N. A.	Patented	[3]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMG 076	DMIKQ40	Obesity	5B81	Discontinued in Phase 1	[4]
NGD-4715	DMXDLUH	Obesity	5B81	Discontinued in Phase 1	[5]
A-798	DMXWG6Z	Obesity	5B81	Terminated	[7]
ALB-127158(a)	DMWNMYS	Obesity	5B81	Terminated	[8]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SNAP-7941	DM5KE4R	Anxiety disorder	6B00-6B0Z	Preclinical	[6]
T-226293	DM7Y4GT	Obesity	5B81	Preclinical	[6]
T-226296	DMJ6P9U	Obesity	5B81	Preclinical	[6]

61 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-phenyl-N,N-bis(o-tolylthiomethyl)ethanamine	DMMJENF	Discovery agent	N.A.	Investigative	[9]
4-arylphthalazin-1(2H)-3,4-Di-F	DM3UE42	Discovery agent	N.A.	Investigative	[10]
7-fluorochromone-2-carboxamide	DMQ2ZTJ	Discovery agent	N.A.	Investigative	[11]
8-(1,2-Dimethyl-propoxy)-quinolin-2-ylamine	DMUE15B	Discovery agent	N.A.	Investigative	[12]
8-(1,3,3-Trimethyl-butoxy)-quinolin-2-ylamine	DMGS7CE	Discovery agent	N.A.	Investigative	[13]
8-(1-Ethyl-propoxy)-quinolin-2-ylamine	DMYERNW	Discovery agent	N.A.	Investigative	[12]
8-(1-Methyl-butoxy)-quinolin-2-ylamine	DM7VT3P	Discovery agent	N.A.	Investigative	[12]
8-(2-Cyclopropyl-ethoxy)-quinolin-2-ylamine	DMJKL3Z	Discovery agent	N.A.	Investigative	[12]
8-(2-Ethoxy-1-methyl-ethoxy)-quinolin-2-ylamine	DMOB8XT	Discovery agent	N.A.	Investigative	[12]
8-(2-Ethyl-1-methyl-butoxy)-quinolin-2-ylamine	DMSKTVW	Discovery agent	N.A.	Investigative	[12]
8-(2-Methoxy-1-methyl-ethoxy)-quinolin-2-ylamine	DMA5K04	Discovery agent	N.A.	Investigative	[12]
8-(2-Methyl-butoxy)-quinolin-2-ylamine	DMVBRMF	Discovery agent	N.A.	Investigative	[12]
8-(2-Methyl-cyclohexyloxy)-quinolin-2-ylamine	DMUIFJY	Discovery agent	N.A.	Investigative	[12]
8-(3,3,3-trifluoropropoxy)quinolin-2-amine	DMRUP0A	Discovery agent	N.A.	Investigative	[12]
8-(3,3-Dimethyl-butoxy)-quinolin-2-ylamine	DM72EM9	Discovery agent	N.A.	Investigative	[12]
8-(3-Methoxy-3-methyl-butoxy)-quinolin-2-ylamine	DM3WEQA	Discovery agent	N.A.	Investigative	[12]
8-(3-Methyl-butoxy)-quinolin-2-ylamine	DMNYPCQ	Discovery agent	N.A.	Investigative	[12]
8-(3-Methyl-cyclohexyloxy)-quinolin-2-ylamine	DMPMJHV	Discovery agent	N.A.	Investigative	[12]
8-(3-Methyl-cyclopentyloxy)-quinolin-2-ylamine	DM8N314	Discovery agent	N.A.	Investigative	[12]
8-(4-Methyl-cyclohexyloxy)-quinolin-2-ylamine	DMPVQN3	Discovery agent	N.A.	Investigative	[12]
8-Butoxy-quinolin-2-ylamine	DM5RFCN	Discovery agent	N.A.	Investigative	[12]
8-Cyclobutylmethoxy-quinolin-2-ylamine	DM4VTM2	Discovery agent	N.A.	Investigative	[12]
8-Cycloheptyloxy-quinolin-2-ylamine	DMEBYRW	Discovery agent	N.A.	Investigative	[12]
8-Cyclohexyloxy-quinolin-2-ylamine	DMKT0YQ	Discovery agent	N.A.	Investigative	[12]
8-Cyclopentylmethoxy-quinolin-2-ylamine	DM16KZS	Discovery agent	N.A.	Investigative	[12]
8-Hexyloxy-quinolin-2-ylamine	DM7PJN9	Discovery agent	N.A.	Investigative	[12]
8-Isopropoxy-quinolin-2-ylamine	DMBIAGJ	Discovery agent	N.A.	Investigative	[12]
8-Methoxy-quinolin-2-ylamine	DMHZ5SB	Discovery agent	N.A.	Investigative	[12]
8-Pentyloxy-quinolin-2-ylamine	DME8S0R	Discovery agent	N.A.	Investigative	[12]
8-Propoxy-quinolin-2-ylamine	DM0TVL5	Discovery agent	N.A.	Investigative	[12]
8-sec-Butoxy-quinolin-2-ylamine	DMFPWJL	Discovery agent	N.A.	Investigative	[12]
A-224940	DM5VQ8E	Discovery agent	N.A.	Investigative	[14]
ADS-102891	DMXD0C3	Discovery agent	N.A.	Investigative	[15]
ADS-103168	DMMYUB9	Discovery agent	N.A.	Investigative	[15]
ADS-103214	DMUMF0B	Discovery agent	N.A.	Investigative	[15]
ADS-103253	DMH9A4S	Discovery agent	N.A.	Investigative	[15]
ADS-103254	DMLIOV2	Discovery agent	N.A.	Investigative	[15]
ADS-103274	DMBN6IE	Discovery agent	N.A.	Investigative	[15]
ADS-103293	DM0C4QD	Discovery agent	N.A.	Investigative	[15]
ADS-103294	DMM2Q9L	Discovery agent	N.A.	Investigative	[15]
ADS-103316	DMKCOYE	Discovery agent	N.A.	Investigative	[15]
AR-129330	DMUSYKG	Discovery agent	N.A.	Investigative	[16]
ATC0065	DMJNQ5G	Discovery agent	N.A.	Investigative	[17]
AZ13483342	DMYDWH1	Discovery agent	N.A.	Investigative	[18]
C3	DMTCOY9	Discovery agent	N.A.	Investigative	[19]
GNF-PF-1550	DMVUBGF	Discovery agent	N.A.	Investigative	[20]
GNF-PF-2322	DMW93IO	Discovery agent	N.A.	Investigative	[20]
GW803430	DMWAEJ3	Discovery agent	N.A.	Investigative	[21]
melanin-concentrating hormone	DMY57L0	Discovery agent	N.A.	Investigative	[22]
MQ1	DMQ357C	Discovery agent	N.A.	Investigative	[23]
N,N-bis(tosylmethyl)hexan-1-amine	DMM678B	Discovery agent	N.A.	Investigative	[9]
N-(1-benzylpiperidin-4-yl)-3,5-dimethoxybenzamide	DM4HB7S	Discovery agent	N.A.	Investigative	[24]
N-(4-amino-2-propylquinolin-6-yl)cinnamamide	DMCLRBK	Discovery agent	N.A.	Investigative	[25]
Phenyl-N,N-bis(tosylmethyl)methanamine	DMYTS73	Discovery agent	N.A.	Investigative	[9]
PMID17125263C17	DMLTXHJ	Discovery agent	N.A.	Investigative	[26]
PMID22490048C(R)-10h	DMQXRCW	Discovery agent	N.A.	Investigative	[27]
pyrrolidine MCHR1 antagonist 1	DME6HCQ	Discovery agent	N.A.	Investigative	[28]
SB-568849	DMBIF42	Discovery agent	N.A.	Investigative	[29]
tetralin_urea analogue (7o)	DMWOBAE	Discovery agent	N.A.	Investigative	[30]
TPI-1361-17	DMW2FTP	Obesity	5B81	Investigative	[31]
[3H]SNAP-7941	DM0MLU9	Discovery agent	N.A.	Investigative	[32]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	6.98E-01	-0.01	-0.04

References

• [1] Phase I clinical trial of AZD1979 for treating obesity. AstraZeneca plc
• [2] 2011 Pipeline of Bristol-Myers Squibb.
• [3] Novel MCH1 receptor antagonists: a patent review.Expert Opin Ther Pat. 2015 Feb;25(2):193-207.
• [4] Stereoselective synthesis of a MCHr1 antagonist. J Org Chem. 2007 Dec 7;72(25):9648-55.
• [5] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [6] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [7] Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function. Endocrinology. 2012 Dec;153(12):6145-54.
• [8] Clinical pipeline report, company report or official report of Albany Molecular Research (2011).
• [9] Discovery of novel chemotypes to a G-protein-coupled receptor through ligand-steered homology modeling and structure-based virtual screening. J Med Chem. 2008 Feb 14;51(3):581-8.
• [10] 4-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.
• [11] Optimization 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.
• [12] Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 1. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4873-7.
• [13] Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 2. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4879-82.
• [14] Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 3. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4883-6.
• [15] Quinazoline and benzimidazole MCH-1R antagonists. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7.
• [16] Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6.
• [17] Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagoni... J Pharmacol Exp Ther. 2005 May;313(2):831-9.
• [18] Discovery 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.
• [19] SLC-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.
• [20] 6-Acylamino-2-aminoquinolines as potent melanin-concentrating hormone 1 receptor antagonists. Identification, structure-activity relationship, and ... J Med Chem. 2005 Sep 8;48(18):5684-97.
• [21] The discovery and optimization of pyrimidinone-containing MCH R1 antagonists. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4723-7.
• [22] [125I]-S36057: a new and highly potent radioligand for the melanin-concentrating hormone receptor. Br J Pharmacol. 2001 Jun;133(3):371-8.
• [23] The 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.
• [24] Identification of substituted 4-aminopiperidines and 3-aminopyrrolidines as potent MCH-R1 antagonists for the treatment of obesity. Bioorg Med Chem Lett. 2006 Oct 15;16(20):5445-50.
• [25] 4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists. Bioorg Med Chem Lett. 2006 Oct 15;16(20):5275-9.
• [26] 6-(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.
• [27] Synthesis, 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.
• [28] Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2460-7.
• [29] Discovery 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.
• [30] Discovery of tetralin ureas as potent melanin concentrating hormone 1 receptor antagonists. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1718-21.
• [31] 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. (Target id: 280).
• [32] Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med. 2002 Aug;8(8):825-30.