Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5LATME)

• DOT Name: REST corepressor 3 (RCOR3)
• Gene Name: RCOR3
• Related Disease:
  Intrahepatic cholangiocarcinoma
  Metastatic malignant neoplasm
  Chronic hepatitis B virus infection
  Hepatitis B virus infection
• UniProt ID: RCOR3_HUMAN
• PDB ID: 4CZZ
• Pfam ID: PF01448 ; PF00249 ; PF20878
• Sequence:
  MRVGAEYQARIPEFDPGATKYTDKDNGGMLVWSPYHSIPDAKLDEYIAIAKEKHGYNVEQ
  ALGMLFWHKHNIEKSLADLPNFTPFPDEWTVEDKVLFEQAFSFHGKSFHRIQQMLPDKTI
  ASLVKYYYSWKKTRSRTSLMDRQARKLANRHNQGDSDDDVEETHPMDGNDSDYDPKKEAK
  KEGNTEQPVQTSKIGLGRREYQSLQHRHHSQRSKCRPPKGMYLTQEDVVAVSCSPNAANT
  ILRQLDMELISLKRQVQNAKQVNSALKQKMEGGIEEFKPPESNQKINARWTTEEQLLAVQ
  GVRKYGKDFQAIADVIGNKTVGQVKNFFVNYRRRFNLEEVLQEWEAEQGTQASNGDASTL
  GEETKSASNVPSGKSTDEEEEAQTPQAPRTLGPSPPAPSSTPTPTAPIATLNQPPPLLRP
  TLPAAPALHRQPPPLQQQARFIQPRPTLNQPPPPLIRPANSMPPRLNPRPVLSTVGGQQP
  PSLIGIQTDSQSSLH
• Function: May act as a component of a corepressor complex that represses transcription.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[1]
Chronic hepatitis B virus infection	DISHL4NT	moderate	Altered Expression	[2]
Hepatitis B virus infection	DISLQ2XY	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of REST corepressor 3 (RCOR3).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of REST corepressor 3 (RCOR3).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of REST corepressor 3 (RCOR3).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of REST corepressor 3 (RCOR3).	[3]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of REST corepressor 3 (RCOR3).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of REST corepressor 3 (RCOR3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of REST corepressor 3 (RCOR3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of REST corepressor 3 (RCOR3).	[10]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of REST corepressor 3 (RCOR3).	[11]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of REST corepressor 3 (RCOR3).	[12]

3 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 decreases the sumoylation of REST corepressor 3 (RCOR3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of REST corepressor 3 (RCOR3).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of REST corepressor 3 (RCOR3).	[8]

References

• [1] Integrated mRNA and lncRNA expression profiling for exploring metastatic biomarkers of human intrahepatic cholangiocarcinoma.Am J Cancer Res. 2017 Mar 1;7(3):688-699. eCollection 2017.
• [2] Involvement of REST corepressor 3 in prognosis of human hepatitis B.Acta Pharmacol Sin. 2011 Aug;32(8):1019-24. doi: 10.1038/aps.2011.49. Epub 2011 Jul 18.
• [3] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [4] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.
• [8] 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.
• [9] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [12] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.