General Information of Drug Off-Target (DOT) (ID: OTBK7278)

DOT Name Protein HEXIM1 (HEXIM1)
Synonyms Cardiac lineage protein 1; Estrogen down-regulated gene 1 protein; Hexamethylene bis-acetamide-inducible protein 1; Menage a quatre protein 1
Gene Name HEXIM1
UniProt ID
HEXI1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2GD7; 3S9G
Pfam ID
PF15313
Sequence
MAEPFLSEYQHQPQTSNCTGAAAVQEELNPERPPGAEERVPEEDSRWQSRAFPQLGGRPG
PEGEGSLESQPPPLQTQACPESSCLREGEKGQNGDDSSAGGDFPPPAEVEPTPEAELLAQ
PCHDSEASKLGAPAAGGEEEWGQQQRQLGKKKHRRRPSKKKRHWKPYYKLTWEEKKKFDE
KQSLRASRIRAEMFAKGQPVAPYNTTQFLMDDHDQEEPDLKTGLYSKRAAAKSDDTSDDD
FMEEGGEEDGGSDGMGGDGSEFLQRDFSETYERYHTESLQNMSKQELIKEYLELEKCLSR
MEDENNRLRLESKRLGGDDARVRELELELDRLRAENLQLLTENELHRQQERAPLSKFGD
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. May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
Tissue Specificity Ubiquitously expressed with higher expression in placenta. HEXIM1 and HEXIM2 are differentially expressed. Expressed in endocrine tissues.

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Protein HEXIM1 (HEXIM1). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Protein HEXIM1 (HEXIM1). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Protein HEXIM1 (HEXIM1). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Protein HEXIM1 (HEXIM1). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Protein HEXIM1 (HEXIM1). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Protein HEXIM1 (HEXIM1). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein HEXIM1 (HEXIM1). [7]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Protein HEXIM1 (HEXIM1). [8]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein HEXIM1 (HEXIM1). [9]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Protein HEXIM1 (HEXIM1). [10]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 increases the expression of Protein HEXIM1 (HEXIM1). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Protein HEXIM1 (HEXIM1). [13]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Protein HEXIM1 (HEXIM1). [14]
Mivebresib DMCPF90 Phase 1 Mivebresib increases the expression of Protein HEXIM1 (HEXIM1). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Protein HEXIM1 (HEXIM1). [16]
I-BET151 DMYRUH2 Investigative I-BET151 increases the expression of Protein HEXIM1 (HEXIM1). [17]
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⏷ Show the Full List of 16 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein HEXIM1 (HEXIM1). [12]
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References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
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 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 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.
5 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.
6 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
7 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
8 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
11 OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Int J Cancer. 2016 Nov 1;139(9):2047-55. doi: 10.1002/ijc.30256. Epub 2016 Jul 30.
12 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.
13 BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget. 2015 Jul 10;6(19):17698-712. doi: 10.18632/oncotarget.4131.
14 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
15 Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
17 Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.