Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8D7CDO)

• DOT Name: Osteoclast-stimulating factor 1 (OSTF1)
• Gene Name: OSTF1
• Related Disease:
  Multiple sclerosis
  Neoplasm
• UniProt ID: OSTF1_HUMAN
• PDB ID: 1X2K; 1ZLM; 3EHQ; 3EHR
• Pfam ID: PF12796 ; PF00018
• Sequence:
  MSKPPPKPVKPGQVKVFRALYTFEPRTPDELYFEEGDIIYITDMSDTNWWKGTSKGRTGL
  IPSNYVAEQAESIDNPLHEAAKRGNLSWLRECLDNRVGVNGLDKAGSTALYWACHGGHKD
  IVEMLFTQPNIELNQQNKLGDTALHAAAWKGYADIVQLLLAKGARTDLRNIEKKLAFDMA
  TNAACASLLKKKQGTDAVRTLSNAEDYLDDEDSD
• Function: Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.
• Tissue Specificity: Ubiquitously expressed. Present in osteoclasts (at protein level).
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[2]

11 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 Osteoclast-stimulating factor 1 (OSTF1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[7]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Osteoclast-stimulating factor 1 (OSTF1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Osteoclast-stimulating factor 1 (OSTF1).	[11]

References

• [1] Association Between Exposure of Ipratropium and Salmeterol and Diagnosis of Multiple Sclerosis: A Matched Case-control Study.Clin Ther. 2019 Aug;41(8):1477-1485. doi: 10.1016/j.clinthera.2019.04.039. Epub 2019 May 23.
• [2] Transcriptome and Proteome Analyses of TNFAIP8 Knockdown Cancer Cells Reveal New Insights into Molecular Determinants of Cell Survival and Tumor Progression.Methods Mol Biol. 2017;1513:83-100. doi: 10.1007/978-1-4939-6539-7_7.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] 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.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.