Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCP792K)

• DOT Name: Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0)
• Synonyms: hnRNP A0
• Gene Name: HNRNPA0
• Related Disease:
  Neoplasm
  Schizophrenia
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Advanced cancer
  Tourette syndrome
• UniProt ID: ROA0_HUMAN
• Pfam ID: PF00076
• Sequence:
  MENSQLCKLFIGGLNVQTSESGLRGHFEAFGTLTDCVVVVNPQTKRSRCFGFVTYSNVEE
  ADAAMAASPHAVDGNTVELKRAVSREDSARPGAHAKVKKLFVGGLKGDVAEGDLIEHFSQ
  FGTVEKAEIIADKQSGKKRGFGFVYFQNHDAADKAAVVKFHPIQGHRVEVKKAVPKEDIY
  SGGGGGGSRSSRGGRGGRGRGGGRDQNGLSKGGGGGYNSYGGYGGGGGGGYNAYGGGGGG
  SSYGGSDYGNGFGGFGSYSQHQSSYGPMKSGGGGGGGGSSWGGRSNSGPYRGGYGGGGGY
  GGSSF
• Function: mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	moderate	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[3]
Lung neoplasm	DISVARNB	moderate	Biomarker	[3]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[4]
Tourette syndrome	DISX9D54	Limited	Unknown	[5]

14 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 Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[13]
Tetracaine	DM9J6C2	Approved	Tetracaine increases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0).	[17]

References

• [1] Knockdown of Hnrnpa0, a del(5q) gene, alters myeloid cell fate in murine cells through regulation of AU-rich transcripts.Haematologica. 2014 Jun;99(6):1032-40. doi: 10.3324/haematol.2013.098657. Epub 2014 Feb 14.
• [2] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [3] Transcriptional analysis of hnRNPA0, A1, A2, B1, and A3 in lung cancer cell lines in response to acidosis, hypoxia, and serum deprivation conditions.Exp Lung Res. 2014 Feb;40(1):12-21. doi: 10.3109/01902148.2013.856049. Epub 2013 Nov 18.
• [4] Mutations of HNRNPA0 and WIF1 predispose members of a large family to multiple cancers.Fam Cancer. 2015 Jun;14(2):297-306. doi: 10.1007/s10689-014-9758-8.
• [5] De novo and inherited private variants in MAP1B in periventricular nodular heterotopia. PLoS Genet. 2018 May 8;14(5):e1007281. doi: 10.1371/journal.pgen.1007281. eCollection 2018 May.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] 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.
• [10] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [11] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [12] 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.
• [13] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [14] Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1. Toxicol Appl Pharmacol. 2022 Jan 1;434:115810. doi: 10.1016/j.taap.2021.115810. Epub 2021 Nov 23.
• [15] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.