Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAJR36W)

• DOT Name: MAPK regulated corepressor interacting protein 2 (MCRIP2)
• Synonyms: Protein FAM195A
• Gene Name: MCRIP2
• UniProt ID: MCRI2_HUMAN
• Pfam ID: PF14799
• Sequence:
  MYTITKGPSKLVAQRRTGPTQQQVEGRLGELLKCRQPAPPTSQPPRAQPFAQPPGPWPLS
  SPGPRLVFNRVNGRRAPSTSPSFEGTQETYTVAHEENVRFVSEAWQQVQQQLDGGPAGEG
  GPRPVQYVERTPNPRLQNFVPIDLDEWWAQQFLARITSCS

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of MAPK regulated corepressor interacting protein 2 (MCRIP2).	[11]

References

• [1] 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.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] 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.
• [12] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.