Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA9WHGF)

• DOT Name: Calpain-7 (CAPN7)
• Synonyms: EC 3.4.22.-; PalB homolog; PalBH
• Gene Name: CAPN7
• Related Disease: Endometriosis
• UniProt ID: CAN7_HUMAN
• PDB ID: 2QFE; 8UC6
• EC Number: 3.4.22.-
• Pfam ID: PF01067 ; PF04212 ; PF00648
• Sequence:
  MDATALERDAVQFARLAVQRDHEGRYSEAVFYYKEAAQALIYAEMAGSSLENIQEKITEY
  LERVQALHSAVQSKSADPLKSKHQLDLERAHFLVTQAFDEDEKENVEDAIELYTEAVDLC
  LKTSYETADKVLQNKLKQLARQALDRAEALSEPLTKPVGKISSTSVKPKPPPVRAHFPLG
  ANPFLERPQSFISPQSCDAQGQRYTAEEIEVLRTTSKINGIEYVPFMNVDLRERFAYPMP
  FCDRWGKLPLSPKQKTTFSKWVRPEDLTNNPTMIYTVSSFSIKQTIVSDCSFVASLAISA
  AYERRFNKKLITGIIYPQNKDGEPEYNPCGKYMVKLHLNGVPRKVIIDDQLPVDHKGELL
  CSYSNNKSELWVSLIEKAYMKVMGGYDFPGSNSNIDLHALTGWIPERIAMHSDSQTFSKD
  NSFRMLYQRFHKGDVLITASTGMMTEAEGEKWGLVPTHAYAVLDIREFKGLRFIQLKNPW
  SHLRWKGRYSENDVKNWTPELQKYLNFDPRTAQKIDNGIFWISWDDLCQYYDVIYLSWNP
  GLFKESTCIHSTWDAKQGPVKDAYSLANNPQYKLEVQCPQGGAAVWVLLSRHITDKDDFA
  NNREFITMVVYKTDGKKVYYPADPPPYIDGIRINSPHYLTKIKLTTPGTHTFTLVVSQYE
  KQNTIHYTVRVYSACSFTFSKIPSPYTLSKRINGKWSGQSAGGCGNFQETHKNNPIYQFH
  IEKTGPLLIELRGPRQYSVGFEVVTVSTLGDPGPHGFLRKSSGDYRCGFCYLELENIPSG
  IFNIIPSTFLPKQEGPFFLDFNSIIPIKITQLQ
• Function: Calcium-regulated non-lysosomal thiol-protease.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometriosis	DISX1AG8	Strong	Biomarker	[1]

11 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 Calpain-7 (CAPN7).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calpain-7 (CAPN7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calpain-7 (CAPN7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calpain-7 (CAPN7).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Calpain-7 (CAPN7).	[6]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Calpain-7 (CAPN7).	[7]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Calpain-7 (CAPN7).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Calpain-7 (CAPN7).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calpain-7 (CAPN7).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Calpain-7 (CAPN7).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calpain-7 (CAPN7).	[11]

References

• [1] Calpain7 impairs embryo implantation by downregulating 3-integrin expression via degradation of HOXA10.Cell Death Dis. 2018 Feb 19;9(3):291. doi: 10.1038/s41419-018-0317-3.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [9] 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.
• [10] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.