Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine-rich repeat-containing protein 75B (LRRC75B)
• Synonyms: Leucine-rich repeat-containing protein FAM211B
• Gene Name: LRRC75B
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: LR75B_HUMAN
• Sequence:
  MGARLGRRAGPEAGSEAGAAAGCGPAPYERRVRWLREIQSTLRERRPERARQLLRLLRQD
  LGLERTLLPDILYRDVAFLNPVDPISHDLLVNLARDLQCPKKDYELWKSSDKICRQLIYH
  LTPHSKQQQGSSLRQRKTQSCLKSSLQKTLLAGETVDLSGIPLSTQDVQHITRYLSSHGA
  VLAVLDLSFTGLSDELLHLLLPSLWALPRLTQLLLNGNRLTRATARKLTDAIKDTTKFPA
  LAWVDLGNNVDVASLPQPLLVGLRRRLSQRTSLPTIYEGLDLEPEGSAAGATTPASTWDS
  TAAGLGPEPQACCAR
• Function: May suppress myogenic differentiation by modulating MYOG expression and Erk1/2 signaling.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Limited	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Leucine-rich repeat-containing protein 75B (LRRC75B).	[13]

References

• [1] A lymph node metastasis-related protein-coding genes combining with long noncoding RNA signature for breast cancer survival prediction.J Cell Physiol. 2019 Nov;234(11):20036-20045. doi: 10.1002/jcp.28600. Epub 2019 Apr 4.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] 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.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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] 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.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] 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.