Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEHK445)

• DOT Name: Cathepsin L2 (CTSV)
• Synonyms: EC 3.4.22.43; Cathepsin U; Cathepsin V
• Gene Name: CTSV
• UniProt ID: CATL2_HUMAN
• PDB ID: 1FH0; 3H6S; 3KFQ; 7PK4; 7Q8D; 7Q8F; 7Q8G; 7Q8H; 7Q8I; 7Q8J; 7Q8K; 7Q8L; 7Q8M; 7Q8N; 7Q8O; 7Q8P; 7Q8Q; 7Q9H; 7QFF; 7QFH; 7QGW; 7QHJ; 7QHK; 7QNS; 7QO2
• EC Number: 3.4.22.43
• Pfam ID: PF08246 ; PF00112
• Sequence:
  MNLSLVLAAFCLGIASAVPKFDQNLDTKWYQWKATHRRLYGANEEGWRRAVWEKNMKMIE
  LHNGEYSQGKHGFTMAMNAFGDMTNEEFRQMMGCFRNQKFRKGKVFREPLFLDLPKSVDW
  RKKGYVTPVKNQKQCGSCWAFSATGALEGQMFRKTGKLVSLSEQNLVDCSRPQGNQGCNG
  GFMARAFQYVKENGGLDSEESYPYVAVDEICKYRPENSVANDTGFTVVAPGKEKALMKAV
  ATVGPISVAMDAGHSSFQFYKSGIYFEPDCSSKNLDHGVLVVGYGFEGANSNNSKYWLVK
  NSWGPEWGSNGYVKIAKDKNNHCGIATAASYPNV
• Function: Cysteine protease. May have an important role in corneal physiology.
• Tissue Specificity: Predominantly expressed in the thymus and testis. Also expressed in corneal epithelium, and to a lesser extent in conjunctival epithelium and skin.
• KEGG Pathway:
  Lysosome (hsa04142)
  Apoptosis (hsa04210)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Trafficking and processing of endosomal TLR (R-HSA-1679131)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  MHC class II antigen presentation (R-HSA-2132295)
  RUNX1 regulates transcription of genes involved in differentiation of keratinocytes (R-HSA-8939242)
  Endosomal/Vacuolar pathway (R-HSA-1236977)

Molecular Interaction Atlas (MIA) of This DOT

16 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 Cathepsin L2 (CTSV).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cathepsin L2 (CTSV).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cathepsin L2 (CTSV).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cathepsin L2 (CTSV).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cathepsin L2 (CTSV).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cathepsin L2 (CTSV).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cathepsin L2 (CTSV).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cathepsin L2 (CTSV).	[7]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Cathepsin L2 (CTSV).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cathepsin L2 (CTSV).	[9]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Cathepsin L2 (CTSV).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cathepsin L2 (CTSV).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cathepsin L2 (CTSV).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cathepsin L2 (CTSV).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cathepsin L2 (CTSV).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cathepsin L2 (CTSV).	[5]

2 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 decreases the methylation of Cathepsin L2 (CTSV).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cathepsin L2 (CTSV).	[13]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] 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.
• [11] 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.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] 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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.