Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNI91K)

• DTT Name: Melanocortin receptor 3 (MC3R)
• Synonyms: MC3-R
• Gene Name: MC3R
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: MC3R_HUMAN
• TTD ID: T76846
• Sequence:
  MNASCCLPSVQPTLPNGSEHLQAPFFSNQSSSAFCEQVFIKPEVFLSLGIVSLLENILVI
  LAVVRNGNLHSPMYFFLCSLAVADMLVSVSNALETIMIAIVHSDYLTFEDQFIQHMDNIF
  DSMICISLVASICNLLAIAVDRYVTIFYALRYHSIMTVRKALTLIVAIWVCCGVCGVVFI
  VYSESKMVIVCLITMFFAMMLLMGTLYVHMFLFARLHVKRIAALPPADGVAPQQHSCMKG
  AVTITILLGVFIFCWAPFFLHLVLIITCPTNPYCICYTAHFNTYLVLIMCNSVIDPLIYA
  FRSLELRNTFREILCGCNGMNLG
• Function: Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Melanotetan II	DMYK8MV	Obesity	5B81	Preclinical	[1]

47 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ac-dR[CEHdFRWC]-NH2	DM7XY41	Discovery agent	N.A.	Investigative	[2]
Ac-His-D-Phe-Arg-2-Nal-NHCH3	DMAQR29	Discovery agent	N.A.	Investigative	[3]
Ac-Nle-c[Asp-His-DNal(2')-Pro-Trp-Lys]-NH2	DMOVI7Y	Discovery agent	N.A.	Investigative	[4]
Ac-R[CEHdFRWC]-NH2	DMBFUD0	Discovery agent	N.A.	Investigative	[2]
Ac-Tyr-D-Phe-Arg-2-Nal-NHCH3	DMIH5CD	Discovery agent	N.A.	Investigative	[3]
Ac-YCit[CEHdFRWC]-NH2	DMAVPXL	Discovery agent	N.A.	Investigative	[2]
Ac-YK[CEHdFRWC]-NH2	DM5SJX8	Discovery agent	N.A.	Investigative	[2]
Ac-YRC(Me)*EHdFRWC(Me)NH2	DMWJ8UR	Discovery agent	N.A.	Investigative	[2]
Ac-YRMEHdFRWG-NH2	DMN2UKC	Discovery agent	N.A.	Investigative	[2]
Ac-YRMEHdFRWGSPPKD-NH2	DMDH5B3	Discovery agent	N.A.	Investigative	[2]
Ac-YR[CEH(d-2alpha-Nal)RWC]-NH2	DMVQ4KG	Discovery agent	N.A.	Investigative	[2]
Ac-YR[CEH(pCl-dF)RWC]-NH2	DM25JXM	Discovery agent	N.A.	Investigative	[2]
Ac-YR[CEH(pF-dF)RWC]-NH2	DMXCF9T	Discovery agent	N.A.	Investigative	[2]
Ac-YR[CEHdFRWC]-NH2	DMBMY73	Discovery agent	N.A.	Investigative	[2]
Ac-YR[CEHdFRWC]SPPKD-NH2	DMDO468	Discovery agent	N.A.	Investigative	[2]
Ac-[CEHdFRWC]-NH2	DMRLOGP	Discovery agent	N.A.	Investigative	[2]
AEKKDEGPYRMEHFRWGSPPKD	DMZ8SV3	Discovery agent	N.A.	Investigative	[2]
C[CO-(CH2)2-CO-Nle-D-Nal(2)-Arg-Trp-Lys]-NH2	DMHARQX	Discovery agent	N.A.	Investigative	[5]
C[CO-(CH2)2-CO-Nle-D-Phe-Arg-Trp-Lys]-NH2	DMI3CSJ	Discovery agent	N.A.	Investigative	[5]
C[CO-(CH2)3-CO-Pro-D-Nal(2)-Arg-Trp-Lys]-NH2	DMYPHVC	Discovery agent	N.A.	Investigative	[5]
C[CO-(CH2)3-CO-Pro-D-Phe-Arg-Trp-Lys]-NH2	DM0VP79	Discovery agent	N.A.	Investigative	[5]
C[CO-2,3-pyrazine-CO-D-Nal(2)-Arg-Trp-Lys]-NH2	DM1VCJP	Discovery agent	N.A.	Investigative	[5]
C[CO-2,3-pyrazine-CO-D-Phe-Arg-Trp-Lys]-NH2	DM8AMGF	Discovery agent	N.A.	Investigative	[5]
C[CO-o-C6H4-CO-Pro-D-Nal(2)-Arg-Trp-Lys]-NH2	DMD6OW4	Discovery agent	N.A.	Investigative	[5]
C[Nle-Arg-D-Nal(2')-Arg-Trp-Glu]-NH2	DMX7IVO	Discovery agent	N.A.	Investigative	[6]
C[Nle-Arg-D-Phe-Arg-Trp-Glu]-NH2	DMUESCH	Discovery agent	N.A.	Investigative	[6]
C[Nle-Asp-D-Nal(2')-Arg-Trp-Glu]-NH2	DM8SXLR	Discovery agent	N.A.	Investigative	[6]
C[Nle-Gln-D-Nal(2')-Arg-Trp-Glu]-NH2	DMM19SJ	Discovery agent	N.A.	Investigative	[6]
C[Nle-Gln-D-Phe-Arg-Trp-Glu]-NH2	DMSGWZE	Discovery agent	N.A.	Investigative	[6]
C[Nle-Glu-D-Nal(2')-Arg-Trp-Glu]-NH2	DMHNCAG	Discovery agent	N.A.	Investigative	[6]
C[Nle-Glu-D-Phe-Arg-Trp-Glu]-NH2	DMVWOPG	Discovery agent	N.A.	Investigative	[6]
C[Nle-His-D-Nal(2')-Arg-Trp-Glu]-NH2	DM36HBK	Discovery agent	N.A.	Investigative	[6]
C[Nle-His-D-Phe-Arg-Trp-Glu]-NH2	DM5HRNM	Discovery agent	N.A.	Investigative	[6]
C[Nle-Nle-D-Nal(2')-Arg-Trp-Glu]-NH2	DM73ZMG	Discovery agent	N.A.	Investigative	[6]
C[Nle-Nle-D-Phe-Arg-Trp-Glu]-NH2	DMDPBVS	Discovery agent	N.A.	Investigative	[6]
C[Nle-Pro-D-Nal(2')-Arg-Trp-Glu]-NH2	DMPZ4VB	Discovery agent	N.A.	Investigative	[6]
C[Nle-Pro-D-Phe-Arg-Trp-Glu]-NH2	DMZWMV0	Discovery agent	N.A.	Investigative	[6]
C[Nle-Val-D-Nal(2')-Arg-Trp-Glu]-NH2	DMSIGJW	Discovery agent	N.A.	Investigative	[6]
C[Nle-Val-D-Phe-Arg-Trp-Glu]-NH2	DM45ZLW	Discovery agent	N.A.	Investigative	[6]
GPYRMEHFRWGSPPKD-NH2	DMLRTPH	Discovery agent	N.A.	Investigative	[2]
MK-10	DMI7859	Discovery agent	N.A.	Investigative	[7]
MK-11	DM4FG32	Discovery agent	N.A.	Investigative	[7]
MK-9	DMKEG2B	Discovery agent	N.A.	Investigative	[5]
MT-II	DMKT1DA	Female sexual arousal dysfunction	HA01.1	Investigative	[8]
NDP-SYSMEHFRWGKPVG	DMRV16G	Discovery agent	N.A.	Investigative	[2]
SHU9119	DMT62LS	Discovery agent	N.A.	Investigative	[9]
Tic-D-Phe-Arg-2-Nal-NHCH3	DMMFCHU	Discovery agent	N.A.	Investigative	[10]

References

• [1] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [2] Discovery of a beta-MSH-derived MC-4R selective agonist. J Med Chem. 2005 May 5;48(9):3095-8.
• [3] Design and synthesis of potent and selective 1,3,4-trisubstituted-2-oxopiperazine based melanocortin-4 receptor agonists. Bioorg Med Chem Lett. 2006 Sep 1;16(17):4668-73.
• [4] Substitution of arginine with proline and proline derivatives in melanocyte-stimulating hormones leads to selectivity for human melanocortin 4 rece... J Med Chem. 2009 Jun 25;52(12):3627-35.
• [5] Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 ... J Med Chem. 2008 Jan 24;51(2):187-95.
• [6] Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities. J Med Chem. 2006 Mar 23;49(6):1946-52.
• [7] Novel cyclic templates of alpha-MSH give highly selective and potent antagonists/agonists for human melanocortin-3/4 receptors. J Med Chem. 2002 Jun 6;45(12):2644-50.
• [8] Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur J Pharmacol. 1999 Aug 13;378(3):249-58.
• [9] Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum. 2002 Oct;46(10):2765-75.
• [10] Synthesis of Tic-D-Phe Psi[CH2-CH2] isostere and its use in the development of melanocortin receptor agonists. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1721-5.