General Information of Drug Therapeutic Target (DTT) (ID: TTG5QB7)

DTT Name Calpain-2 (CAPN2)
Synonyms
Millimolar-calpain; M-calpain; Calpain-2 large subunit; Calpain-2 catalytic subunit; Calpain large polypeptide L2; Calpain M-type; Calcium-activated neutral proteinase 2; Calcium-activated neutral proteinase; CANPL2; CANP 2; CANP
Gene Name CAPN2
DTT Type
Clinical trial target
[1]
BioChemical Class
Peptidase
UniProt ID
CAN2_HUMAN
TTD ID
T04902
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.4.22.53
Sequence
MAGIAAKLAKDREAAEGLGSHDRAIKYLNQDYEALRNECLEAGTLFQDPSFPAIPSALGF
KELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEI
LARVVPLNQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSAL
LEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELKKPPPNLFKIIQKALQKGSLLGC
SIDITSAADSEAITFQKLVKGHAYSVTGAEEVESNGSLQKLIRIRNPWGEVEWTGRWNDN
CPSWNTIDPEERERLTRRHEDGEFWMSFSDFLRHYSRLEICNLTPDTLTSDTYKKWKLTK
MDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDEEDGESGCTFLVGLIQKHRRRQR
KMGEDMHTIGFGIYEVPEELSGQTNIHLSKNFFLTNRARERSDTFINLREVLNRFKLPPG
EYILVPSTFEPNKDGDFCIRVFSEKKADYQAVDDEIEANLEEFDISEDDIDDGFRRLFAQ
LAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYIL
WTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKMPCQLHQVIVARFADDQLIIDFD
NFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLCFSVL
Function
Proteolytically cleaves MYOC at 'Arg-226'. Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs. Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
KEGG Pathway
Protein processing in endoplasmic reticulum (hsa04141 )
Apoptosis (hsa04210 )
Alzheimer's disease (hsa05010 )
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ABT-957 DMB9N4J Alzheimer disease 8A20 Phase 1 [1]
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19 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
5-azolone derivative 1 DMN2B87 N. A. N. A. Patented [2]
Carboxamide derivative 10 DM5WMO9 N. A. N. A. Patented [2]
Carboxamide derivative 11 DM1DN94 N. A. N. A. Patented [2]
Carboxamide derivative 5 DM149WN N. A. N. A. Patented [2]
Carboxamide derivative 6 DM6GZW4 N. A. N. A. Patented [2]
Carboxamide derivative 7 DM8TQS4 N. A. N. A. Patented [2]
Carboxamide derivative 8 DM6HI34 N. A. N. A. Patented [2]
Carboxamide derivative 9 DMVISYC N. A. N. A. Patented [2]
Epoxysuccinate derivative 1 DMU8LPN N. A. N. A. Patented [2]
Epoxysuccinate derivative 10 DMYF39U N. A. N. A. Patented [2]
Epoxysuccinate derivative 2 DMEV9O3 N. A. N. A. Patented [2]
Epoxysuccinate derivative 3 DMMETW5 N. A. N. A. Patented [2]
Epoxysuccinate derivative 4 DMCF6M8 N. A. N. A. Patented [2]
Epoxysuccinate derivative 5 DM37MCN N. A. N. A. Patented [2]
Epoxysuccinate derivative 6 DMQM6ZS N. A. N. A. Patented [2]
Epoxysuccinate derivative 7 DMTSPVF N. A. N. A. Patented [2]
Epoxysuccinate derivative 8 DMQTVPC N. A. N. A. Patented [2]
Epoxysuccinate derivative 9 DM49FU0 N. A. N. A. Patented [2]
PMID25399719-Compound-17 DMRXKJZ N. A. N. A. Patented [2]
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⏷ Show the Full List of 19 Patented Agent(s)
5 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
BITHIONOL DMPJKRL Trematode infection 1F8Y Withdrawn from market [3]
Aloxistatin DMGW07M Neurological disorder 6B60 Discontinued in Phase 3 [3]
AK-295 DM51NI0 Cerebral infarction 8B11.5Z Terminated [4]
MDL-28170 DMYK31O Alzheimer disease 8A20 Terminated [5]
SJA-6017 DM6X430 N. A. N. A. Terminated [6]
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12 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(1-Benzyl-2-oxo-ethyl)-carbamic acid benzyl ester DMWK3RO Discovery agent N.A. Investigative [7]
3-(1H-Pyrrol-3-yl)-propionamide DMCKJ27 Discovery agent N.A. Investigative [8]
A-558693 DMN320E Neurological disorder 6B60 Investigative [4]
AW-00430 DMG6LJ8 Discovery agent N.A. Investigative [3]
Calpastatin DMR0CNQ Discovery agent N.A. Investigative [9]
DIHYDROXANTHOHUMOL DMFKWRM Discovery agent N.A. Investigative [3]
GNF-PF-4453 DMPYIA3 Discovery agent N.A. Investigative [3]
mercaptoacrylate inhibitor of calpain 1 DMZIA1R Discovery agent N.A. Investigative [4]
N-(1-Benzyl-2-oxo-ethyl)-benzamide DMP9A7L Discovery agent N.A. Investigative [7]
PMID20690647C4b DMKVONZ Discovery agent N.A. Investigative [10]
PMID20690647C5a DMRWZX6 Discovery agent N.A. Investigative [10]
PMID8831774C19 DMM08LV Discovery agent N.A. Investigative [11]
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⏷ Show the Full List of 12 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Alzheimer's disease 8A00.0 Entorhinal cortex 5.15E-14 0.35 1.04
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References

1 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
2 An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
3 In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2336).
5 Synthesis of a small library of diketopiperazines as potential inhibitors of calpain. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3034-8.
6 Synthesis, biological evaluation and molecular modelling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors. Bioorg Med Chem. 2008 Jul 15;16(14):6911-23.
7 Alpha-diketone and alpha-keto ester derivatives of N-protected amino acids and peptides as novel inhibitors of cysteine and serine proteinases. J Med Chem. 1990 Jan;33(1):11-3.
8 Synthesis of cystamidin a (pyrrole-3-propanamide), a reported calpain inhibitor, Bioorg. Med. Chem. Lett. 6(13):1541-1542 (1996).
9 Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Brain Res Rev. 2003 May;42(2):169-85.
10 Peptidyl alpha-ketoamides with nucleobases, methylpiperazine, and dimethylaminoalkyl substituents as calpain inhibitors. J Med Chem. 2010 Sep 9;53(17):6326-36.
11 Novel peptidyl alpha-keto amide inhibitors of calpains and other cysteine proteases. J Med Chem. 1996 Sep 27;39(20):4089-98.