Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI56YTK)

• DOT Name: Cathepsin F (CTSF)
• Synonyms: CATSF; EC 3.4.22.41
• Gene Name: CTSF
• Related Disease:
  Adult neuronal ceroid lipofuscinosis
  Neuronal ceroid lipofuscinosis 13
• UniProt ID: CATF_HUMAN
• PDB ID: 1M6D
• EC Number: 3.4.22.41
• Pfam ID: PF08246 ; PF00112
• Sequence:
  MAPWLQLLSLLGLLPGAVAAPAQPRAASFQAWGPPSPELLAPTRFALEMFNRGRAAGTRA
  VLGLVRGRVRRAGQGSLYSLEATLEEPPCNDPMVCRLPVSKKTLLCSFQVLDELGRHVLL
  RKDCGPVDTKVPGAGEPKSAFTQGSAMISSLSQNHPDNRNETFSSVISLLNEDPLSQDLP
  VKMASIFKNFVITYNRTYESKEEARWRLSVFVNNMVRAQKIQALDRGTAQYGVTKFSDLT
  EEEFRTIYLNTLLRKEPGNKMKQAKSVGDLAPPEWDWRSKGAVTKVKDQGMCGSCWAFSV
  TGNVEGQWFLNQGTLLSLSEQELLDCDKMDKACMGGLPSNAYSAIKNLGGLETEDDYSYQ
  GHMQSCNFSAEKAKVYINDSVELSQNEQKLAAWLAKRGPISVAINAFGMQFYRHGISRPL
  RPLCSPWLIDHAVLLVGYGNRSDVPFWAIKNSWGTDWGEKGYYYLHRGSGACGVNTMASS
  AVVD
• Function: Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
• Tissue Specificity: High expression levels in heart, skeletal muscle, brain, testis and ovary; moderate levels in prostate, placenta, liver and colon; and no detectable expression in peripheral leukocytes and thymus.
• KEGG Pathway:
  Lysosome (hsa04142)
  Apoptosis (hsa04210)
• Reactome Pathway: MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult neuronal ceroid lipofuscinosis	DIS5UHAA	Definitive	Autosomal recessive	[1]
Neuronal ceroid lipofuscinosis 13	DISZGTC7	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cathepsin F (CTSF).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cathepsin F (CTSF).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cathepsin F (CTSF).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cathepsin F (CTSF).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cathepsin F (CTSF).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cathepsin F (CTSF).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cathepsin F (CTSF).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Cathepsin F (CTSF).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cathepsin F (CTSF).	[12]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Cathepsin F (CTSF).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cathepsin F (CTSF).	[11]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [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] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.