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 | |||||
Ref 530396 | Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527195 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527196 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 527194 | Bioorg 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 552787 | The medicinal chemistry of agents targeting monoacylglycerol lipase. Curr Top Med Chem. 2008;8(3):231-46. | ||||
Ref 528381 | Bioorg Med Chem Lett. 2006 Oct 15;16(20):5275-9. Epub 2006 Aug 17.4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists. | ||||
Ref 529257 | J 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 527713 | J 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 529257 | J 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 530316 | Bioorg 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 530316 | Bioorg 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 530316 | Bioorg 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 529257 | J 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 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528347 | Bioorg 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 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. |
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