Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB95LIK)

• DOT Name: Melanocyte-stimulating hormone receptor (MC1R)
• Synonyms: MSH-R; Melanocortin receptor 1; MC1-R
• Gene Name: MC1R
• UniProt ID: MSHR_HUMAN
• PDB ID: 7F4D; 7F4F; 7F4H; 7F4I
• Pfam ID: PF00001
• Sequence:
  MAVQGSQRRLLGSLNSTPTAIPQLGLAANQTGARCLEVSISDGLFLSLGLVSLVENALVV
  ATIAKNRNLHSPMYCFICCLALSDLLVSGSNVLETAVILLLEAGALVARAAVLQQLDNVI
  DVITCSSMLSSLCFLGAIAVDRYISIFYALRYHSIVTLPRARRAVAAIWVASVVFSTLFI
  AYYDHVAVLLCLVVFFLAMLVLMAVLYVHMLARACQHAQGIARLHKRQRPVHQGFGLKGA
  VTLTILLGIFFLCWGPFFLHLTLIVLCPEHPTCGCIFKNFNLFLALIICNAIIDPLIYAF
  HSQELRRTLKEVLTCSW
• Function: Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Mediates melanogenesis, the production of eumelanin (black/brown) and phaeomelanin (red/yellow), via regulation of cAMP signaling in melanocytes.
• Tissue Specificity: Expressed in melanocytes . Expressed in corticoadrenal tissue .
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Melanogenesis (hsa04916)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

18 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[2]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Melanocyte-stimulating hormone receptor (MC1R).	[3]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[4]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[9]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[4]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[12]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid increases the expression of Melanocyte-stimulating hormone receptor (MC1R).	[7]

References

• [1] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [2] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [3] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [4] Examining the impact of skin lighteners in vitro. Oxid Med Cell Longev. 2013;2013:702120. doi: 10.1155/2013/702120. Epub 2013 Apr 28.
• [5] Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology. 2007 Jun;121(2):266-75. doi: 10.1111/j.1365-2567.2007.02574.x. Epub 2007 Mar 7.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] The essential role of p53 in hyperpigmentation of the skin via regulation of paracrine melanogenic cytokine receptor signaling. J Biol Chem. 2009 Feb 13;284(7):4343-53. doi: 10.1074/jbc.M805570200. Epub 2008 Dec 18.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.