Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8J4J5E)

• DOT Name: Leucine-rich repeat-containing protein 14 (LRRC14)
• Gene Name: LRRC14
• UniProt ID: LRC14_HUMAN
• Pfam ID: PF13516
• Sequence:
  MHTLVFLSTRQVLQCQPAACQALPLLPRELFPLLFKVAFMDKKTVVLRELVHTWPFPLLS
  FQQLLQECAHCSRALLQERPSTESMQAVILGLTARLHTSEPGASTQPLCRKHALRVLDMT
  GLLDDGVEQDPGTMSMWDCTAAVARTCIAQQQGGAAEPGPAPIPVEVRVDLRVNRASYAF
  LREALRSSVGSPLRLCCRDLRAEDLPMRNTVALLQLLDAGCLRRVDLRFNNLGLRGLSVI
  IPHVARFQHLASLRLHYVHGDSRQPSVDGEDNFRYFLAQMGRFTCLRELSMGSSLLSGRL
  DQLLSTLQSPLESLELAFCALLPEDLRFLARSPHAAHLKKLDLSGNDLSGSQLAPFQGLL
  QASAATLLHLELTECQLADTQLLATLPILTQCASLRYLGLYGNPLSMAGLKELLRDSVAQ
  AELRTVVHPFPVDCYEGLPWPPPASVLLEASINEEKFARVEAELHQLLLASGRAHVLWTT
  DIYGRLAADYFSL
• Function: Negatively regulates Toll-like receptor-mediated NF-kappa-B signaling by disrupting IKK core complex formation through interaction with IKBKB.
• Reactome Pathway: Regulation of NF-kappa B signaling (R-HSA-9758274)

Molecular Interaction Atlas (MIA) of This DOT

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 Leucine-rich repeat-containing protein 14 (LRRC14).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine-rich repeat-containing protein 14 (LRRC14).	[7]

6 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 Leucine-rich repeat-containing protein 14 (LRRC14).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Leucine-rich repeat-containing protein 14 (LRRC14).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Leucine-rich repeat-containing protein 14 (LRRC14).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Leucine-rich repeat-containing protein 14 (LRRC14).	[5]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Leucine-rich repeat-containing protein 14 (LRRC14).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Leucine-rich repeat-containing protein 14 (LRRC14).	[8]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.