Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJNQRC5)

• DOT Name: Ligand-dependent nuclear receptor corepressor-like protein (LCORL)
• Synonyms: LCoR-like protein
• Gene Name: LCORL
• Related Disease:
  Cardiovascular disease
  Squamous cell carcinoma
  Lung squamous cell carcinoma
• UniProt ID: LCORL_HUMAN
• Pfam ID: PF05225
• Sequence:
  MDKGRERMAAAAAAAAAAAAAAQCRSPRCAAERRGFRRELDSWRHRLMHCVGFESILEGL
  YGPRLRRDLSLFEDCEPEELTDWSMDEKCSFCNLQREAVSDCIPSLDSSQSTPTEELSSQ
  GQSNTDKIECQAENYLNALFRKKDLPQNCDPNIPLVAQELMKKMIRQFAIEYISKSGKTQ
  ENRNGSIGPSIVCKSIQMNQAENSLQEEQEGPLDLTVNRMQEQNTQQGDGVLDLSTKKTS
  IKSEESSICDPSSENSVAGRLHRNREDYVERSAEFADGLLSKALKDIQSGALDINKAGIL
  YGIPQKTLLLHLEALPAGKPASFKNKTRDFHDSYSYKDSKETCAVLQKVALWARAQAERT
  EKSKLNLLETSEIKFPTASTYLHQLTLQKMVTQFKEKNESLQYETSNPTVQLKIPQLRVS
  SVSKSQPDGSGLLDVMYQVSKTSSVLEGSALQKLKNILPKQNKIECSGPVTHSSVDSYFL
  HGDLSPLCLNSKNGTVDGTSENTEDGLDRKDSKQPRKKRGRYRQYDHEIMEEAIAMVMSG
  KMSVSKAQGIYGVPHSTLEYKVKERSGTLKTPPKKKLRLPDTGLYNMTDSGTGSCKNSSK
  PV
• Function: May act as transcription activator that binds DNA elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. May play a role in spermatogenesis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[2]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[2]

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 Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[9]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[12]

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 affects the methylation of Ligand-dependent nuclear receptor corepressor-like protein (LCORL).	[11]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] 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.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.