Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQA7Z5H)

• DOT Name: Cotranscriptional regulator ARB2A (ARB2A)
• Synonyms: ARB2 cotranscriptional regulator A; Cotranscriptional regulator FAM172A; Protein FAM172A
• Gene Name: ARB2A
• UniProt ID: ARB2A_HUMAN
• Pfam ID: PF09757
• Sequence:
  MSISLSSLILLPIWINMAQIQQGGPDEKEKTTALKDLLSRIDLDELMKKDEPPLDFPDTL
  EGFEYAFNEKGQLRHIKTGEPFVFNYREDLHRWNQKRYEALGEIITKYVYELLEKDCNLK
  KVSIPVDATESEPKSFIFMSEDALTNPQKLMVLIHGSGVVRAGQWARRLIINEDLDSGTQ
  IPFIKRAVAEGYGVIVLNPNENYIEVEKPKIHVQSSSDSSDEPAEKRERKDKVSKETKKR
  RDFYEKYRNPQREKEMMQLYIRENGSPEEHAIYVWDHFIAQAAAENVFFVAHSYGGLAFV
  ELMIQREADVKNKVTAVALTDSVHNVWHQEAGKTIREWMRENCCNWVSSSEPLDTSVESM
  LPDCPRVSAGTDRHELTSWKSFPSIFKFFTEASEAKTSSLKPAVTRRSHRIKHEEL
• Function: Plays a role in the regulation of alternative splicing, by interacting with AGO2 and CHD7. Seems to be required for stabilizing protein-protein interactions at the chromatin-spliceosome interface. May have hydrolase activity.

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 decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[9]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cotranscriptional regulator ARB2A (ARB2A).	[12]

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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.