Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM9H8HD)

• DOT Name: Ras-related protein Rab-42 (RAB42)
• Gene Name: RAB42
• Related Disease: Glioma
• UniProt ID: RAB42_HUMAN
• Pfam ID: PF00071
• Sequence:
  MEAEGCRYQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEPEPEPTVGAECYRRALQLRA
  GPRVKLQLWDTAGHERFRCITRSFYRNVVGVLLVFDVTNRKSFEHIQDWHQEVMATQGPD
  KVIFLLVGHKSDLQSTRCVSAQEAEELAASLGMAFVETSVKNNCNVDLAFDTLADAIQQA
  LQQGDIKLEEGWGGVRLIHKTQIPRSPSRKQHSGPCQC
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ras-related protein Rab-42 (RAB42).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-related protein Rab-42 (RAB42).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras-related protein Rab-42 (RAB42).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ras-related protein Rab-42 (RAB42).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ras-related protein Rab-42 (RAB42).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-42 (RAB42).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Rab-42 (RAB42).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras-related protein Rab-42 (RAB42).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ras-related protein Rab-42 (RAB42).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-related protein Rab-42 (RAB42).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-related protein Rab-42 (RAB42).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related protein Rab-42 (RAB42).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related protein Rab-42 (RAB42).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ras-related protein Rab-42 (RAB42).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras-related protein Rab-42 (RAB42).	[15]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Ras-related protein Rab-42 (RAB42).	[16]

References

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• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] 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.
• [13] 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.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [15] 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.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.