Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGZWL4N)

• DOT Name: Protein HEXIM2 (HEXIM2)
• Synonyms: Hexamethylene bis-acetamide-inducible protein 2
• Gene Name: HEXIM2
• UniProt ID: HEXI2_HUMAN
• Pfam ID: PF15313
• Sequence:
  MMATPNQTACNAESPVALEEAKTSGAPGSPQTPPERHDSGGSLPLTPRMESHSEDEDLAG
  AVGGLGWNSRSPRTQSPGGCSAEAVLARKKHRRRPSKRKRHWRPYLELSWAEKQQRDERQ
  SQRASRVREEMFAKGQPVAPYNTTQFLMNDRDPEEPNLDVPHGISHPGSSGESEAGDSDG
  RGRAHGEFQRKDFSETYERFHTESLQGRSKQELVRDYLELEKRLSQAEEETRRLQQLQAC
  TGQQSCRQVEELAAEVQRLRTENQRLRQENQMWNREGCRCDEEPGT
• Function: Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation.
• Tissue Specificity: Ubiquitously expressed with higher expression in testis. HEXIM1 and HEXIM2 are differentially expressed.

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 Protein HEXIM2 (HEXIM2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein HEXIM2 (HEXIM2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein HEXIM2 (HEXIM2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein HEXIM2 (HEXIM2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein HEXIM2 (HEXIM2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein HEXIM2 (HEXIM2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein HEXIM2 (HEXIM2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein HEXIM2 (HEXIM2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein HEXIM2 (HEXIM2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein HEXIM2 (HEXIM2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein HEXIM2 (HEXIM2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein HEXIM2 (HEXIM2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein HEXIM2 (HEXIM2).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein HEXIM2 (HEXIM2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein HEXIM2 (HEXIM2).	[14]

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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Epigenetic reader BRD4 inhibition as a therapeutic strategy to suppress E2F2-cell cycle regulation circuit in liver cancer. Oncotarget. 2016 May 31;7(22):32628-40. doi: 10.18632/oncotarget.8701.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.