Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSJ29M5)

• DOT Name: Leucine rich adaptor protein 1-like (LURAP1L)
• Gene Name: LURAP1L
• Related Disease:
  Ankylosing spondylitis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  Coeliac disease
  Common variable immunodeficiency
  Crohn disease
  Juvenile idiopathic arthritis
  Psoriasis
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Type-1 diabetes
  Ulcerative colitis
• UniProt ID: LUR1L_HUMAN
• Pfam ID: PF14854
• Sequence:
  MEDSPLPDLRDIELKLGRKVPESLVRSLRGEEPVPRERDRDPCGGSGGGGGGGGGCSSSS
  SYCSFPPSLSSSSSSSPTSGSPRGSHSSALERLETKLHLLRQEMVNLRATDVRLMRQLLV
  INESIESIKWMIEEKATITSRGSSLSGSLCSLLESQSTSLRGSYNSLHDGSDGLDGISVG
  SYLDTLADDVPGHQTPSDLDQFSDSSLIEDSQALHKRPKLDSEYYCFG

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ankylosing spondylitis	DISRC6IR	moderate	Genetic Variation	[1]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[1]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[1]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[1]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[1]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[1]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[1]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Genetic Variation	[1]
Psoriasis	DIS59VMN	moderate	Genetic Variation	[1]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[1]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[1]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[1]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[1]

2 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 adaptor protein 1-like (LURAP1L).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Leucine rich adaptor protein 1-like (LURAP1L).	[6]

15 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 adaptor protein 1-like (LURAP1L).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Leucine rich adaptor protein 1-like (LURAP1L).	[17]

References

• [1] Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nat Med. 2015 Sep;21(9):1018-27. doi: 10.1038/nm.3933. Epub 2015 Aug 24.
• [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] Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro. 2009 Apr;23(3):486-99.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [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] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.