Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK6OQZR)

• DOT Name: Calpain-1 catalytic subunit (CAPN1)
• Synonyms: EC 3.4.22.52; Calcium-activated neutral proteinase 1; CANP 1; Calpain mu-type; Calpain-1 large subunit; Cell proliferation-inducing gene 30 protein; Micromolar-calpain; muCANP
• Gene Name: CAPN1
• Related Disease: Autosomal recessive spastic paraplegia type 76
• UniProt ID: CAN1_HUMAN
• PDB ID: 1ZCM; 2ARY; 7W7O; 7X79; 8GX3
• EC Number: 3.4.22.52
• Pfam ID: PF01067 ; PF13833 ; PF00648
• Sequence:
  MSEEIITPVYCTGVSAQVQKQRARELGLGRHENAIKYLGQDYEQLRVRCLQSGTLFRDEA
  FPPVPQSLGYKDLGPNSSKTYGIKWKRPTELLSNPQFIVDGATRTDICQGALGDCWLLAA
  IASLTLNDTLLHRVVPHGQSFQNGYAGIFHFQLWQFGEWVDVVVDDLLPIKDGKLVFVHS
  AEGNEFWSALLEKAYAKVNGSYEALSGGSTSEGFEDFTGGVTEWYELRKAPSDLYQIILK
  ALERGSLLGCSIDISSVLDMEAITFKKLVKGHAYSVTGAKQVNYRGQVVSLIRMRNPWGE
  VEWTGAWSDSSSEWNNVDPYERDQLRVKMEDGEFWMSFRDFMREFTRLEICNLTPDALKS
  RTIRKWNTTLYEGTWRRGSTAGGCRNYPATFWVNPQFKIRLDETDDPDDYGDRESGCSFV
  LALMQKHRRRERRFGRDMETIGFAVYEVPPELVGQPAVHLKRDFFLANASRARSEQFINL
  REVSTRFRLPPGEYVVVPSTFEPNKEGDFVLRFFSEKSAGTVELDDQIQANLPDEQVLSE
  EEIDENFKALFRQLAGEDMEISVKELRTILNRIISKHKDLRTKGFSLESCRSMVNLMDRD
  GNGKLGLVEFNILWNRIRNYLSIFRKFDLDKSGSMSAYEMRMAIESAGFKLNKKLYELII
  TRYSEPDLAVDFDNFVCCLVRLETMFRFFKTLDTDLDGVVTFDLFKWLQLTMFA
• Function: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409'. Cleaves and activates caspase-7 (CASP7).
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
  Cellular senescence (hsa04218)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Shigellosis (hsa05131)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Formation of the cornified envelope (R-HSA-6809371)
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  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
Autosomal recessive spastic paraplegia type 76	DIS18ARV	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calpain-1 catalytic subunit (CAPN1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calpain-1 catalytic subunit (CAPN1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Calpain-1 catalytic subunit (CAPN1).	[23]

25 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 Calpain-1 catalytic subunit (CAPN1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calpain-1 catalytic subunit (CAPN1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Calpain-1 catalytic subunit (CAPN1).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Calpain-1 catalytic subunit (CAPN1).	[12]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[13]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Calpain-1 catalytic subunit (CAPN1).	[14]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Calpain-1 catalytic subunit (CAPN1).	[15]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Calpain-1 catalytic subunit (CAPN1).	[16]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Calpain-1 catalytic subunit (CAPN1).	[17]
Glimepiride	DM5FSJA	Approved	Glimepiride increases the expression of Calpain-1 catalytic subunit (CAPN1).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[21]
MDL-28170	DMYK31O	Terminated	MDL-28170 decreases the activity of Calpain-1 catalytic subunit (CAPN1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[24]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[25]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Calpain-1 catalytic subunit (CAPN1).	[26]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[27]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Calpain-1 catalytic subunit (CAPN1).	[28]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Calpain-1 catalytic subunit (CAPN1).	[29]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Calpain-1 catalytic subunit (CAPN1).	[30]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the cleavage of Calpain-1 catalytic subunit (CAPN1).	[9]

References

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• [11] Cannabidiol Modulates the Expression of Alzheimer's Disease-Related Genes in Mesenchymal Stem Cells. Int J Mol Sci. 2016 Dec 23;18(1):26. doi: 10.3390/ijms18010026.
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• [13] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
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