Therapeutic Targets Database
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TTD Target ID: TTDC00072

Target Information
NameMelanocortin-4 receptor    
Type of targetClinical trial target    
SynonymsMC4-R    
DiseaseErectile Dysfunction
[ICD9: 302.72, 607.84   ICD10: F52.2, N48.4]
[1][2][3]
Obesity
[ICD9: 278   ICD10: E66]
[4]
Sexual Dysfunction, Female
[ICD9: 302.7   ICD10: F52]
[1][2][3]
Drug(s)BremelanotidePhase IIbErectile Dysfunction[1][2][3]
BremelanotidePhase IIaSexual Dysfunction, Female[1][2][3]
CHIR-01020PreclinicalObesity[5]
IDDBCP-150101PreclinicalObesity, Sexual dysfunction[5]
MC-4 agonistPreclinicalObesity[5]
Melanotetan IIPreclinicalSexual dysfunction, Obesity, Type 2 diabetes[5]
PT-15PreclinicalSexual dysfunction, Obesity[5]
RM-493PreclinicalObesity, diabetes[6]
Ro-27-3225PreclinicalObesity[5]
BioChemical ClassG-protein coupled receptor (rhodopsin family)    
PathwayNeuroactive ligand-receptor interaction
UniProt IDP32245
PDB Structure2IQP; 2IQR; 2IQS; 2IQU; 2IQV; 2IQW.    
FunctionReceptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-msh. This receptor is mediated by G proteins that stimulates adenylate cyclase.    
SequenceMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLL ENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVN IDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVS GILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGAN MKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPL IYALRSQELRKTFKEIICCYPLGGLCDLSSRY
Related US Patent6,350,760
6,376,509
6,472,398
6,600,015
6,767,915
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor1-Benzyl-4-methyl-piperazine[7]
1-Methyl-4- (1-phenyl-ethyl)-piperazine[7]
4- (4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one[8]
AC-Nle-c[Asp-His-DPhe-Pro-Trp-Lys]-NH2[9]
AEKKDEGPYRMEHFRWGSPPKD[10]
Ac-His-D-Phe-Arg-2-Nal-NHCH3[11]
Ac-His-DPhe-Arg-Trp-NH2[12]
Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2[13]
Ac-Nle-c[Asp-His-DNaI (2')-Pro-Trp-Lys]-NH2[9]
Ac-Nle-c[Asp-His-DNal (2')-Pro-Trp-Lys]-NH2[9]
Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2[9]
Ac-Phe-[Orn-Pro-cha-Trp-Arg][14]
Ac-R[CEHdFRWC]-NH2[10]
Ac-Tyr-D-Phe-Arg-2-Nal-NHCH3[11]
Ac-YCit[CEHdFRWC]-NH2[10]
Ac-YK[CEHdFRWC]-NH2[10]
Ac-YRC (Me)*EHdFRWC[10]
Ac-YRMEHdFRWG-NH2[10]
Ac-YRMEHdFRWGSPPKD-NH2[10]
Ac-YR[CE (1-Me-H)dFRWC]-NH2[10]
Ac-YR[CEH (d-2alpha-Nal)RWC]-NH2[10]
Ac-YR[CEH (pCl-dF)RWC]-NH2[10]
Ac-YR[CEH (pF-dF)RWC]-NH2[10]
Ac-YR[CEHFRWC]-NH2[10]
Ac-YR[CEHdFRWC]-NH2[10]
Ac-YR[CEHdFRWC]SPPKD-NH2[10]
Ac-[CEHdFRWC]-NH2[10]
Ac-dR[CEHdFRWC]-NH2[10]
Alpha-MSH[15]
D-Phe-Arg-2-Nal-NHCH3[16]
D-Phe-Arg-2-Nal-NHCH3[11]
GPYRMEHFRWGSPPKD-NH2[10]
His-DPhe-Arg-Trp[17]
Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2[14]
MCL-129[18]
MK-10[19]
MK-11[19]
ML-253764[20]
NDP-SYSMEHFRWGKPVG[10]
NDP-alpha-MSH[21]
Ser-Tyr-Ser-Nle-Glu-His-Dphe-Arg[17]
Tic-D-Phe-Arg-2-Nal-NHCH3[22]
c (his-D-phe-arg-trp-Abu)[23]
c (his-D-phe-arg-trp-Ahp)[23]
c (his-D-phe-arg-trp-Ahx)[23]
c (his-D-phe-arg-trp-Aoc)[23]
c (his-L-phe-arg-trp-Aoc)[23]
c[CO- (CH2)2-CO-Nle-D-Nal[13]
c[CO- (CH2)2-CO-Nle-D-Phe-Arg-Trp-Lys]-NH2[13]
c[CO- (CH2)3-CO-Pro-D-Nal[13]
c[CO-o-C6H4-CO-Pro-D-Nal (2)-Arg-Trp-Lys]-NH2[13]
c[CO-o-C6H4-CO-Pro-D-Phe-Arg-Trp-Lys]-NH2[13]
c[Nle-Arg-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Arg-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Nle-Asp-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Asp-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Nle-Gln-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Glu-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-His-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-His-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Nle-Nle-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Nle-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Nle-Pro-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Pro-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Nle-Val-D-Nal (2')-Arg-Trp-Glu]-NH2[24]
c[Nle-Val-D-Phe-Arg-Trp-Glu]-NH2[24]
c[Ser-Tyr-Thr-His-Dphe-Arg-Trp-Thr-Ile-Pro][20]
c[Thr-Tyr-Thr-His-DNaf-Arg-Trp-Thr-Ile-Pro][20]
AgonistAMSH[25]
Amylin[4]
Bremelanotide[1][2][3]
CHIR-01020[5]
IDDBCP-150101[5]
MC-4 agonist[5]
MTII Melanotan-II[25]
Melanotetan II[5]
PT-15[5]
RM-493[6]
Ro-27-3225[5]
AntagonistHS014[26]
Melanocortin-4 Receptor antagonist[27]
MultitargetMelanotetan II[5]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. To Reference
Ref 2Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):383-408. To Reference
Ref 3Clinical applications of centrally acting agents in male sexual dysfunction. Int J Impot Res. 2008 Jul;20 Suppl 1:S17-23. To Reference
Ref 4Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26. To Reference
Ref 5Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60. To Reference
Ref 62011 Pipeline of Ipsen. To Reference
Ref 7Bioorg Med Chem Lett. 2005 Nov 15;15(22):4973-8.Privileged structure based ligands for melanocortin receptors--substituted benzylic piperazine derivatives. To Reference
Ref 8J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 9J Med Chem. 2009 Jun 25;52(12):3627-35.Substitution of arginine with proline and proline derivatives in melanocyte-stimulating hormones leads to selectivity for human melanocortin 4 receptor. To Reference
Ref 10J Med Chem. 2005 May 5;48(9):3095-8.Discovery of a beta-MSH-derived MC-4R selective agonist. To Reference
Ref 11Bioorg Med Chem Lett. 2006 Sep 1;16(17):4668-73.Design and synthesis of potent and selective 1,3,4-trisubstituted-2-oxopiperazine based melanocortin-4 receptor agonists. To Reference
Ref 12J Med Chem. 1997 Jul 4;40(14):2133-9.Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R. To Reference
Ref 13J Med Chem. 2008 Jan 24;51(2):187-95. Epub 2007 Dec 19.Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor. To Reference
Ref 14Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. Epub 2006 Jul 28.Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. To Reference
Ref 15Bioorg Med Chem Lett. 2005 Aug 1;15(15):3501-5.Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist. To Reference
Ref 16J Med Chem. 2006 Jul 27;49(15):4745-61.Design, synthesis, and evaluation of proline and pyrrolidine based melanocortin receptor agonists. A conformationally restricted dipeptide mimic approach. To Reference
Ref 17Bioorg Med Chem Lett. 2007 Jun 15;17(12):3310-3. Epub 2007 Apr 6.Squalene-derived flexible linkers for bioactive peptides. To Reference
Ref 18Bioorg Med Chem. 2007 Mar 1;15(5):1989-2005. Epub 2006 Dec 30.Structure-activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor. To Reference
Ref 19J Med Chem. 2002 Jun 6;45(12):2644-50.Novel cyclic templates of alpha-MSH give highly selective and potent antagonists/agonists for human melanocortin-3/4 receptors. To Reference
Ref 20J Med Chem. 2006 Feb 9;49(3):911-22.Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation. To Reference
Ref 21J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia. To Reference
Ref 22Bioorg Med Chem Lett. 2006 Mar 15;16(6):1721-5. Epub 2005 Dec 20.Synthesis of Tic-D-Phe Psi[CH2-CH2] isostere and its use in the development of melanocortin receptor agonists. To Reference
Ref 23Bioorg Med Chem Lett. 2006 Jul 15;16(14):3723-6. Epub 2006 May 5.Design of cyclic peptides with agonist activity at melanocortin receptor-4. To Reference
Ref 24J Med Chem. 2006 Mar 23;49(6):1946-52.Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities. To Reference
Ref 25Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. Epub 2007 Aug 27. To Reference
Ref 26Long-term administration of MC4 receptor antagonist HS014 causes hyperphagia and obesity in rats. Neuroreport. 1999 Mar 17;10(4):707-11. To Reference
Ref 27Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36. To Reference



 

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