Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT57EOE)

• DOT Name: Melanin-concentrating hormone receptor 1 (MCHR1)
• Synonyms: MCH receptor 1; MCH-R1; MCHR-1; G-protein coupled receptor 24; MCH-1R; MCH1R; MCHR; SLC-1; Somatostatin receptor-like protein
• Gene Name: MCHR1
• UniProt ID: MCHR1_HUMAN
• Pfam ID: PF00001
• Sequence:
  MDLEASLLPTGPNASNTSDGPDNLTSAGSPPRTGSISYINIIMPSVFGTICLLGIIGNST
  VIFAVVKKSKLHWCNNVPDIFIINLSVVDLLFLLGMPFMIHQLMGNGVWHFGETMCTLIT
  AMDANSQFTSTYILTAMAIDRYLATVHPISSTKFRKPSVATLVICLLWALSFISITPVWL
  YARLIPFPGGAVGCGIRLPNPDTDLYWFTLYQFFLAFALPFVVITAAYVRILQRMTSSVA
  PASQRSIRLRTKRVTRTAIAICLVFFVCWAPYYVLQLTQLSISRPTLTFVYLYNAAISLG
  YANSCLNPFVYIVLCETFRKRLVLSVKPAAQGQLRAVSNAQTADEERTESKGT
• Function: Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
• Tissue Specificity: Highest level in brain, particularly in the frontal cortex and hypothalamus, lower levels in the liver and heart.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  BBSome-mediated cargo-targeting to cilium (R-HSA-5620922)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[1]
Manganese	DMKT129	Investigative	Manganese increases the expression of Melanin-concentrating hormone receptor 1 (MCHR1).	[11]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Haloperidol	DM96SE0	Approved	Haloperidol affects the binding of Melanin-concentrating hormone receptor 1 (MCHR1).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanin-concentrating hormone receptor 1 (MCHR1).	[10]

References

• [1] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. doi: 10.1038/sj.tpj.6500418. Epub 2006 Sep 19.
• [9] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.