Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMEB9QG)

• DOT Name: Integral membrane protein GPR137C (GPR137C)
• Synonyms: Transmembrane 7 superfamily member 1-like 2 protein
• Gene Name: GPR137C
• UniProt ID: G137C_HUMAN
• Sequence:
  MRVSVPGPAAAAAPAAGREPSTPGGGSGGGGAVAAASGAAVPGSVQLALSVLHALLYAAL
  FAFAYLQLWRLLLYRERRLSYQSLCLFLCLLWAALRTTLFSAAFSLSGSLPLLRPPAHLH
  FFPHWLLYCFPSCLQFSTLCLLNLYLAEVICKVRCATELDRHKILLHLGFIMASLLFLVV
  NLTCAMLVHGDVPENQLKWTVFVRALINDSLFILCAISLVCYICKITKMSSANVYLESKG
  MSLCQTVVVGSVVILLYSSRACYNLVVVTISQDTLESPFNYGWDNLSDKAHVEDISGEEY
  IVFGMVLFLWEHVPAWSVVLFFRAQRLNQNLAPAGMINSHSYSSRAYFFDNPRRYDSDDD
  LPRLGSSREGSLPNSQSLGWYGTMTGCGSSSYTVTPHLNGPMTDTAPLLFTCSNLDLNNH
  HSLYVTPQN
• Function: Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.

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 Integral membrane protein GPR137C (GPR137C).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Integral membrane protein GPR137C (GPR137C).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Integral membrane protein GPR137C (GPR137C).	[3]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Integral membrane protein GPR137C (GPR137C).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Integral membrane protein GPR137C (GPR137C).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Integral membrane protein GPR137C (GPR137C).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Integral membrane protein GPR137C (GPR137C).	[7]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Integral membrane protein GPR137C (GPR137C).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Integral membrane protein GPR137C (GPR137C).	[1]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Integral membrane protein GPR137C (GPR137C).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Integral membrane protein GPR137C (GPR137C).	[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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.