Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9JMKX)

• DOT Name: Leucine-rich repeat-containing protein 58 (LRRC58)
• Gene Name: LRRC58
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: LRC58_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MEEAGAAVVTAGEAELNWSRLSVSTETLESELEARGEERRGAREALLRLLLPHNRLVSLP
  RALGSGFPHLQLLDVSGNALTALGPELLALRGLRTLLAKNNRLGGPSALPKGLAQSPLCR
  SLQVLNLSGNCFQEVPASLLELRALQTLSLGGNQLQSIPAEIENLQSLECLYLGGNFIKE
  IPPELGNLPSLNYLVLCDNKIQSIPPQLSQLHSLRSLSLHNNLLTYLPREILNLIHLEEL
  SLRGNPLVVRFVRDLTYDPPTLLELAARTIKIRNISYTPYDLPGNLLRYLGSASNCPNPK
  CGGVYFDCCVRQIKFVDFCGKYRLPLMHYLCSPECSSPCSSASHSSTSQSESDSEDEASV
  AARRMQKVLLG

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Limited	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[12]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[2]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[15]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Leucine-rich repeat-containing protein 58 (LRRC58).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich repeat-containing protein 58 (LRRC58).	[6]

References

• [1] Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Dis Markers. 2015;2015:241301. doi: 10.1155/2015/241301. Epub 2015 Sep 28.
• [2] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.