Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTETUZ64)

• DOT Name: G patch domain-containing protein 2-like (GPATCH2L)
• Gene Name: GPATCH2L
• UniProt ID: GPT2L_HUMAN
• Sequence:
  MDELVHDLASALEQTSEQNKLGELWEEMALSPRQQRRQLRKRRGRKRRSDFTHLAEHTCC
  YSEASESSLDEATKDCREVAPVTNFSDSDDTMVAKRHPALNAIVKSKQHSWHESDSFTEN
  APCRPLRRRRKVKRVTSEVAASLQQKLKVSDWSYERGCRFKSAKKQRLSRWKENTPWTSS
  GHGLCESAENRTFLSKTGRKERMECETDEQKQGSDENMSECETSSVCSSSDTGLFTNDEG
  RQGDDEQSDWFYEGECVPGFTVPNLLPKWAPDHCSEVERMDSGLDKFSDSTFLLPSRPAQ
  RGYHTRLNRLPGAAARCLRKGRRRLVGKETSINTLGTERISHIISDPRQKEKNKALASDF
  PHISACAHEFNPLSPLYSLDVLADASHRRCSPAHCSARQANVHWGPPCSRDIKRKRKPVA
  TASLSSPSAVHMDAVEPTTPASQAPKSPSSEWLVRTSAAEKATDATTATFFKMPQEKSPG
  YS

Molecular Interaction Atlas (MIA) of This DOT

15 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 G patch domain-containing protein 2-like (GPATCH2L).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of G patch domain-containing protein 2-like (GPATCH2L).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of G patch domain-containing protein 2-like (GPATCH2L).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of G patch domain-containing protein 2-like (GPATCH2L).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] 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.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.