Target Validation Information
Target ID T09572
Target Name Melanin-concentrating hormone receptor 1
Target Type
Clinical Trial
Drug Potency against Target AR-129330 Drug Info IC50 = 7.2 nM [530396]
ADS-103274 Drug Info IC50 = 28 nM [528581]
ADS-103214 Drug Info IC50 = 9 nM [528581]
ADS-103316 Drug Info IC50 = 41 nM [528581]
ADS-103293 Drug Info IC50 = 1930 nM [528581]
8-Cyclobutylmethoxy-quinolin-2-ylamine Drug Info IC50 = 432 nM [527194]
8-(4-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info IC50 = 349 nM [527194]
8-sec-Butoxy-quinolin-2-ylamine Drug Info IC50 = 5310 nM [527194]
8-Isopropoxy-quinolin-2-ylamine Drug Info IC50 = 437 nM [527194]
8-(1-Ethyl-propoxy)-quinolin-2-ylamine Drug Info IC50 = 326 nM [527194]
8-(1,3,3-Trimethyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 210 nM [527195]
8-Propoxy-quinolin-2-ylamine Drug Info IC50 = 1100 nM [527194]
8-(2-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info IC50 = 1330 nM [527194]
8-(3-Methyl-cyclohexyloxy)-quinolin-2-ylamine Drug Info IC50 = 640 nM [527194]
8-(3,3-Dimethyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 201 nM [527194]
8-Butoxy-quinolin-2-ylamine Drug Info IC50 = 789 nM [527194]
8-Cyclopentylmethoxy-quinolin-2-ylamine Drug Info IC50 = 2290 nM [527194]
8-(2-Methyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 36 nM [527194]
A-224940 Drug Info IC50 = 1680 nM [527196]
8-(2-Ethyl-1-methyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 1300 nM [527194]
8-(2-Ethoxy-1-methyl-ethoxy)-quinolin-2-ylamine Drug Info IC50 = 1070 nM [527194]
8-Cyclohexyloxy-quinolin-2-ylamine Drug Info IC50 = 361 nM [527194]
8-Pentyloxy-quinolin-2-ylamine Drug Info IC50 = 580 nM [527194]
8-Hexyloxy-quinolin-2-ylamine Drug Info IC50 = 818 nM [527194]
8-(3-Methyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 614 nM [527194]
8-Cycloheptyloxy-quinolin-2-ylamine Drug Info IC50 = 3480 nM [527194]
8-(2-Methoxy-1-methyl-ethoxy)-quinolin-2-ylamine Drug Info IC50 = 606 nM [527194]
8-(1,2-Dimethyl-propoxy)-quinolin-2-ylamine Drug Info IC50 = 199 nM [527194]
8-(1-Methyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 860 nM [527194]
8-(3,3,3-trifluoropropoxy)quinolin-2-amine Drug Info IC50 = 722 nM [527194]
8-(3-Methyl-cyclopentyloxy)-quinolin-2-ylamine Drug Info IC50 = 823 nM [527194]
8-(2-Cyclopropyl-ethoxy)-quinolin-2-ylamine Drug Info IC50 = 492 nM [527194]
8-(3-Methoxy-3-methyl-butoxy)-quinolin-2-ylamine Drug Info IC50 = 132 nM [527194]
8-Methoxy-quinolin-2-ylamine Drug Info IC50 = 1590 nM [527194]
T-226296 Drug Info IC50 = 5.5 nM [552787]
N-(4-amino-2-propylquinolin-6-yl)cinnamamide Drug Info IC50 = 1000 nM [528381]
2-phenyl-N,N-bis(o-tolylthiomethyl)ethanamine Drug Info Ki = 7500 nM [529257]
GNF-PF-1550 Drug Info IC50 = 16 nM [527713]
Phenyl-N,N-bis(tosylmethyl)methanamine Drug Info Ki = 7500 nM [529257]
AMG 076 Drug Info IC50 = 0.9~24 nM [530316]
NGD-4715 Drug Info IC50 = 0.9~24 nM [530316]
N,N-bis(tosylmethyl)hexan-1-amine Drug Info Ki = 1700 nM [529257]
ADS-103253 Drug Info IC50 = 58 nM [528581]
N-(1-benzylpiperidin-4-yl)-3,5-dimethoxybenzamide Drug Info Ki = 302 nM [528347]
ADS-103294 Drug Info IC50 = 101 nM [528581]
ADS-103168 Drug Info IC50 = 9 nM [528581]
ADS-102891 Drug Info IC50 = 100 nM [528581]
ADS-103254 Drug Info IC50 = 164 nM [528581]
Action against Disease Model AMG 076 MCH-1R antagonists such as GW856464,AMG-07619 and and NGD-4715 produced anti-obese effects in diet-induced obese (DIO) rats [530316] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Since the MCH receptor-1 (MCH-R1), the only functional receptor that mediates MCH functions in rodents, facilitates behavioral performance in hippocampus-dependent learning tasks, we investigated whether glutamatergic transmission in CA1 pyramidal cells could be modulated in mice lacking the MCH-R1 gene (MCH-R1(-/-)). We found that both |?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor-mediated transmissions were diminished in the mutant mice compared with their controls. This deficit was explained, at least in part, bya postsynaptic down-regulation of these receptors since the amplitude of miniature excitatory postsynaptic currents and the NMDA/AMPA ratio were decreased. Long-term synaptic potentiation (LTP) was also impaired in MCH-R1(-/-) mice. This was due to an altered induction, rather than an impaired, expression because repeating the induction stimulus restored LTP to a normal magnitude. In addition, long-term synaptic depression was strongly diminished in MCH-R1(-/-) mice. These results suggest that MCH exerts a facilitatory effect on CA1 glutamatergic synaptic transmission and long-term synaptic plasticity. Recently, it has been shown that MCH neurons fire exclusively during sleep and mainly during rapid eye movement sleep. Thus these findings provide a mechanism by which sleep might facilitate memory consolidation [530396]
References
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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 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.
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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 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 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 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.
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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 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 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 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 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 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.
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Ref 552787The medicinal chemistry of agents targeting monoacylglycerol lipase. Curr Top Med Chem. 2008;8(3):231-46.
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 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 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 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 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 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 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 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.
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 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.
Ref 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.
Ref 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.
Ref 528581Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists.

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