Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH4KQPI)

• DOT Name: Probable G-protein coupled receptor 27 (GPR27)
• Synonyms: Super conserved receptor expressed in brain 1
• Gene Name: GPR27
• Related Disease: Malignant mesothelioma
• UniProt ID: GPR27_HUMAN
• Pfam ID: PF00001
• Sequence:
  MANASEPGGSGGGEAAALGLKLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDL
  CLADGLRALACLPAVMLAARRAAAAAGAPPGALGCKLLAFLAALFCFHAAFLLLGVGVTR
  YLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGDDEDAPCALEQRPDGA
  PGALGFLLLLAVVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAA
  NWTAGFGRGPTPPALVGIRPAGPGRGARRLLVLEEFKTEKRLCKMFYAVTLLFLLLWGPY
  VVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCFRAQFPCCQSPR
  TTQATHPCDLKGIGL
• Function: Orphan receptor. Possible candidate for amine-like G-protein coupled receptor.
• Tissue Specificity: Highly expressed as a 3.0 kb transcript in brain, ovary, testis, heart, prostate and peripheral Leukocytes. Lower levels in pancreas and small intestine. A 2.3 kb transcript was also found in peripheral Leukocytes. In brain regions, detected as a 3.0 kb transcript in all regions tested. Highest levels in the caudate nucleus, putamen, hippocampus and subthalamic nucleus. Lowest level in the cerebellum.
• Reactome Pathway: G alpha (s) signalling events (R-HSA-418555)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable G-protein coupled receptor 27 (GPR27).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Probable G-protein coupled receptor 27 (GPR27).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable G-protein coupled receptor 27 (GPR27).	[8]

References

• [1] MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.