Target Information

Target General Infomation
Target ID
T04902
Former ID
TTDR00505
Target Name
Calpain
Gene Name
CAPN2
Synonyms
CANP; Calcium-activated neutral proteinase; CAPN2
Target Type
Clinical Trial
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Cerebral infarction [ICD10: I63]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Trematode infection [ICD10: B66.9]
Function
Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
BioChemical Class
Peptidase
Target Validation
T04902
UniProt ID
P17655
EC Number
EC 3.4.22.52
Sequence
MAGIAAKLAKDREAAEGLGSHDRAIKYLNQDYEALRNECLEAGTLFQDPSFPAIPSALGF
KELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEI
LARVVPLNQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSAL
LEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELKKPPPNLFKIIQKALQKGSLLGC
SIDITSAADSEAITFQKLVKGHAYSVTGAEEVESNGSLQKLIRIRNPWGEVEWTGRWNDN
CPSWNTIDPEERERLTRRHEDGEFWMSFSDFLRHYSRLEICNLTPDTLTSDTYKKWKLTK
MDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDEEDGESGCTFLVGLIQKHRRRQR
KMGEDMHTIGFGIYEVPEELSGQTNIHLSKNFFLTNRARERSDTFINLREVLNRFKLPPG
EYILVPSTFEPNKDGDFCIRVFSEKKADYQAVDDEIEANLEEFDISEDDIDDGFRRLFAQ
LAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYIL
WTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKMPCQLHQVIVARFADDQLIIDFD
NFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLCFSVL
Structure
1KFU; 1KFX; 2NQA; 1ZCM; 2ARY
Drugs and Mode of Action
Drug(s) ABT-957 Drug Info Phase 1 Alzheimer disease [1]
BITHIONOL Drug Info Withdrawn from market Trematode infection [2], [3]
Aloxistatin Drug Info Discontinued in Phase 3 Neurological disease [4]
AK-295 Drug Info Terminated Cerebral infarction [5]
MDL-2170 Drug Info Terminated Discovery agent [6]
MDL-28170 Drug Info Terminated Alzheimer disease [6]
SJA-6017 Drug Info Terminated Discovery agent [7]
Inhibitor (1-Benzyl-2-oxo-ethyl)-carbamic acid benzyl ester Drug Info [8]
3-(1H-Pyrrol-3-yl)-propionamide Drug Info [9]
A-558693 Drug Info [10]
AK-295 Drug Info [10]
Aloxistatin Drug Info [11]
AW-00430 Drug Info [11]
BITHIONOL Drug Info [11]
Calpastatin Drug Info [12], [13]
compound 19 Drug Info [14]
compound 4b Drug Info [15]
compound 5a Drug Info [15]
DIHYDROXANTHOHUMOL Drug Info [11]
GNF-PF-4453 Drug Info [11]
MDL-2170 Drug Info [16]
MDL-28170 Drug Info [17]
mercaptoacrylate inhibitor of calpain 1 Drug Info [10]
N-(1-Benzyl-2-oxo-ethyl)-benzamide Drug Info [8]
SJA-6017 Drug Info [18]
Modulator ABT-957 Drug Info [19]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Protein processing in endoplasmic reticulum
Apoptosis
Alzheimer&#039
s disease
Reactome Degradation of the extracellular matrix
WikiPathways Focal Adhesion
Integrated Pancreatic Cancer Pathway
Alzheimers Disease
Integrin-mediated Cell Adhesion
References
REF 1ClinicalTrials.gov (NCT02220738) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ABT-957 in Subjects With Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors. U.S. National Institutes of Health.
REF 2(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. (Ligand id: 2338).
REF 3Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 4Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002441)
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007674)
REF 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003692)
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008985)
REF 8J Med Chem. 1990 Jan;33(1):11-3.Alpha-diketone and alpha-keto ester derivatives of N-protected amino acids and peptides as novel inhibitors of cysteine and serine proteinases.
REF 9Synthesis of cystamidin a (pyrrole-3-propanamide), a reported calpain inhibitor, Bioorg. Med. Chem. Lett. 6(13):1541-1542 (1996).
REF 10(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).
REF 11Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
REF 12Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Brain Res Rev. 2003 May;42(2):169-85.
REF 13PEST sequences in the malaria parasite Plasmodium falciparum: a genomic study. Malar J. 2003 Jun 23;2:16. Epub 2003 Jun 23.
REF 14Novel peptidyl alpha-keto amide inhibitors of calpains and other cysteine proteases. J Med Chem. 1996 Sep 27;39(20):4089-98.
REF 15Peptidyl alpha-ketoamides with nucleobases, methylpiperazine, and dimethylaminoalkyl substituents as calpain inhibitors. J Med Chem. 2010 Sep 9;53(17):6326-36.
REF 16Bioorg Med Chem Lett. 2009 Jan 15;19(2):502-7. Epub 2008 Nov 14.Design and synthesis of 4-aryl-4-oxobutanoic acid amides as calpain inhibitors.
REF 17Bioorg Med Chem Lett. 2005 Jun 15;15(12):3034-8.Synthesis of a small library of diketopiperazines as potential inhibitors of calpain.
REF 18Bioorg Med Chem. 2008 Jul 15;16(14):6911-23. Epub 2008 May 27.Synthesis, biological evaluation and molecular modelling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors.
REF 19Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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