Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFL6VRO)

• DOT Name: Cathepsin O (CTSO)
• Synonyms: EC 3.4.22.42
• Gene Name: CTSO
• Related Disease:
  Breast cancer
  Metastatic malignant neoplasm
  Breast carcinoma
• UniProt ID: CATO_HUMAN
• EC Number: 3.4.22.42
• Pfam ID: PF00112
• Sequence:
  MDVRALPWLPWLLWLLCRGGGDADSRAPFTPTWPRSREREAAAFRESLNRHRYLNSLFPS
  ENSTAFYGINQFSYLFPEEFKAIYLRSKPSKFPRYSAEVHMSIPNVSLPLRFDWRDKQVV
  TQVRNQQMCGGCWAFSVVGAVESAYAIKGKPLEDLSVQQVIDCSYNNYGCNGGSTLNALN
  WLNKMQVKLVKDSEYPFKAQNGLCHYFSGSHSGFSIKGYSAYDFSDQEDEMAKALLTFGP
  LVVIVDAVSWQDYLGGIIQHHCSSGEANHAVLITGFDKTGSTPYWIVRNSWGSSWGVDGY
  AHVKMGSNVCGIADSVSSIFV
• Function: Proteolytic enzyme possibly involved in normal cellular protein degradation and turnover.
• Tissue Specificity: Expressed in all tissues examined. High levels seen in the ovary, kidney and placenta while low levels seen in thymus and skeletal muscle.
• KEGG Pathway:
  Lysosome (hsa04142)
  Apoptosis (hsa04210)
• Reactome Pathway: MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[1]

1 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 Cathepsin O (CTSO).	[3]

16 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 Cathepsin O (CTSO).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cathepsin O (CTSO).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cathepsin O (CTSO).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cathepsin O (CTSO).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cathepsin O (CTSO).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cathepsin O (CTSO).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cathepsin O (CTSO).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Cathepsin O (CTSO).	[10]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Cathepsin O (CTSO).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cathepsin O (CTSO).	[12]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Cathepsin O (CTSO).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cathepsin O (CTSO).	[14]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Cathepsin O (CTSO).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cathepsin O (CTSO).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Cathepsin O (CTSO).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Cathepsin O (CTSO).	[18]

References

• [1] SNPs near the cysteine proteinase cathepsin O gene (CTSO) determine tamoxifen sensitivity in ER-positive breast cancer through regulation of BRCA1.PLoS Genet. 2017 Oct 2;13(10):e1007031. doi: 10.1371/journal.pgen.1007031. eCollection 2017 Oct.
• [2] Potential markers of tongue tumor progression selected by cDNA microarray.Int J Immunopathol Pharmacol. 2005 Jul-Sep;18(3):513-24. doi: 10.1177/039463200501800311.
• [3] 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.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [9] 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.
• [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] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [12] 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.
• [13] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [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] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [16] 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.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] 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.