Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ02075)

• DOT Name: Leucine-rich repeat-containing protein 42 (LRRC42)
• Gene Name: LRRC42
• Related Disease:
  Lung cancer
  Lung carcinoma
• UniProt ID: LRC42_HUMAN
• Pfam ID: PF13516
• Sequence:
  MSYYLSSENHLDPGPIYMRENGQLHMVNLALDGVRSSLQKPRPFRLFPKGFSVELCMNRE
  DDTARKEKTDHFIFTYTREGNLRYSAKSLFSLVLGFISDNVDHIDSLIGFPEQIAEKLFS
  AAEARQKFTEPGAGLRALQKFTEAYGSLVLCSLCLRNRYLVISEKLEEIKSFRELTCLDL
  SCCKLGDEHELLEHLTNEALSSVTQLHLKDNCLSDAGVRKMTAPVRVMKRGLENLTLLDL
  SCNPEITDAGIGYLFSFRKLNCLDISGTGLKDIKTVKHKLQTHIGLVHSKVPLKEFDHSN
  CKTEGWADQIVLQWERVTAEAVKPRETSEPRAAAQRFYGKRSRAEAPLKCPLADTHMNSS
  EKLQFYKEKAPDCHGPVLKHEAISSQESKKSKKRPFEESETEQNNSSQPSKQKYVCLAVE
  DWDLLNSY

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	moderate	Biomarker	[1]
Lung carcinoma	DISTR26C	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Leucine-rich repeat-containing protein 42 (LRRC42).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leucine-rich repeat-containing protein 42 (LRRC42).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Leucine-rich repeat-containing protein 42 (LRRC42).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Leucine-rich repeat-containing protein 42 (LRRC42).	[10]

References

• [1] Identification of a nuclear protein, LRRC42, involved in lung carcinogenesis.Int J Oncol. 2014 Jul;45(1):147-56. doi: 10.3892/ijo.2014.2418. Epub 2014 May 6.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [8] 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.
• [9] 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.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.