Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVK7PK3)

• DOT Name: Coronin-2A (CORO2A)
• Synonyms: IR10; WD repeat-containing protein 2
• Gene Name: CORO2A
• Related Disease:
  Adenocarcinoma
  Colon carcinoma
  Colorectal adenoma
• UniProt ID: COR2A_HUMAN
• Pfam ID: PF08953 ; PF00400 ; PF16300
• Sequence:
  MSWHPQYRSSKFRHVFGKPASKENCYDSVPITRSVHDNHFCAVNPHFIAVVTECAGGGAF
  LVIPLHQTGKLDPHYPKVCGHRGNVLDVKWNPFDDFEIASCSEDATIKIWSIPKQLLTRN
  LTAYRKELVGHARRVGLVEWHPTAANILFSAGYDYKVMIWNLDTKESVITSPMSTISCHQ
  DVILSMSFNTNGSLLATTCKDRKIRVIDPRAGTVLQEASYKGHRASKVLFLGNLKKLMST
  GTSRWNNRQVALWDQDNLSVPLMEEDLDGSSGVLFPFYDADTSMLYVVGKGDGNIRYYEV
  SADKPHLSYLTEYRSYNPQKGIGVMPKRGLDVSSCEIFRFYKLITTKSLIEPISMIVPRR
  SESYQEDIYPPTAGAQPSLTAQEWLSGMNRDPILVSLRPGSELLRPHPLPAERPIFNSMA
  PASPRLLNQTEKLAAEDGWRSSSLLEEKMPRWAAEHRLEEKKTWLTNGFDVFECPPPKTE
  NELLQMFYRQQEEIRRLRELLTQREVQAKQLELEIKNLRMGSEQL

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Coronin-2A (CORO2A).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coronin-2A (CORO2A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coronin-2A (CORO2A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Coronin-2A (CORO2A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coronin-2A (CORO2A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coronin-2A (CORO2A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coronin-2A (CORO2A).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Coronin-2A (CORO2A).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Coronin-2A (CORO2A).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Coronin-2A (CORO2A).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coronin-2A (CORO2A).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Coronin-2A (CORO2A).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Coronin-2A (CORO2A).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Coronin-2A (CORO2A).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Coronin-2A (CORO2A).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Coronin-2A (CORO2A).	[11]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Coronin-2A (CORO2A).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coronin-2A (CORO2A).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Coronin-2A (CORO2A).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Coronin-2A (CORO2A).	[18]

References

• [1] Coronin 2A (CRN5) expression is associated with colorectal adenoma-adenocarcinoma sequence and oncogenic signalling.BMC Cancer. 2015 Sep 15;15:638. doi: 10.1186/s12885-015-1645-7.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] 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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.