Target Information
| Target General Information | Top | |||||
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| Target ID |
T04902
(Former ID: TTDR00505)
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| Target Name |
Calpain-2 (CAPN2)
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| 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
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| Gene Name |
CAPN2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| 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.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.53
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| Sequence |
MAGIAAKLAKDREAAEGLGSHDRAIKYLNQDYEALRNECLEAGTLFQDPSFPAIPSALGF
KELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEI LARVVPLNQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSAL LEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELKKPPPNLFKIIQKALQKGSLLGC SIDITSAADSEAITFQKLVKGHAYSVTGAEEVESNGSLQKLIRIRNPWGEVEWTGRWNDN CPSWNTIDPEERERLTRRHEDGEFWMSFSDFLRHYSRLEICNLTPDTLTSDTYKKWKLTK MDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDEEDGESGCTFLVGLIQKHRRRQR KMGEDMHTIGFGIYEVPEELSGQTNIHLSKNFFLTNRARERSDTFINLREVLNRFKLPPG EYILVPSTFEPNKDGDFCIRVFSEKKADYQAVDDEIEANLEEFDISEDDIDDGFRRLFAQ LAGEDAEISAFELQTILRRVLAKRQDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYIL WTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKMPCQLHQVIVARFADDQLIIDFD NFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLCFSVL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | ABT-957 | Drug Info | Phase 1 | Alzheimer disease | [2] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | BITHIONOL | Drug Info | Withdrawn from market | Trematode infection | [3], [4] | |
| 2 | Aloxistatin | Drug Info | Discontinued in Phase 3 | Neurological disorder | [5] | |
| 3 | AK-295 | Drug Info | Terminated | Cerebral infarction | [6] | |
| 4 | MDL-28170 | Drug Info | Terminated | Alzheimer disease | [7] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | ABT-957 | Drug Info | [1] | |||
| Inhibitor | [+] 36 Inhibitor drugs | + | ||||
| 1 | 5-azolone derivative 1 | Drug Info | [8] | |||
| 2 | Carboxamide derivative 10 | Drug Info | [8] | |||
| 3 | Carboxamide derivative 11 | Drug Info | [8] | |||
| 4 | Carboxamide derivative 5 | Drug Info | [8] | |||
| 5 | Carboxamide derivative 6 | Drug Info | [8] | |||
| 6 | Carboxamide derivative 7 | Drug Info | [8] | |||
| 7 | Carboxamide derivative 8 | Drug Info | [8] | |||
| 8 | Carboxamide derivative 9 | Drug Info | [8] | |||
| 9 | Epoxysuccinate derivative 1 | Drug Info | [8] | |||
| 10 | Epoxysuccinate derivative 10 | Drug Info | [8] | |||
| 11 | Epoxysuccinate derivative 2 | Drug Info | [8] | |||
| 12 | Epoxysuccinate derivative 3 | Drug Info | [8] | |||
| 13 | Epoxysuccinate derivative 4 | Drug Info | [8] | |||
| 14 | Epoxysuccinate derivative 5 | Drug Info | [8] | |||
| 15 | Epoxysuccinate derivative 6 | Drug Info | [8] | |||
| 16 | Epoxysuccinate derivative 7 | Drug Info | [8] | |||
| 17 | Epoxysuccinate derivative 8 | Drug Info | [8] | |||
| 18 | Epoxysuccinate derivative 9 | Drug Info | [8] | |||
| 19 | PMID25399719-Compound-17 | Drug Info | [8] | |||
| 20 | BITHIONOL | Drug Info | [9] | |||
| 21 | Aloxistatin | Drug Info | [9] | |||
| 22 | AK-295 | Drug Info | [10] | |||
| 23 | MDL-28170 | Drug Info | [11] | |||
| 24 | SJA-6017 | Drug Info | [12] | |||
| 25 | (1-Benzyl-2-oxo-ethyl)-carbamic acid benzyl ester | Drug Info | [13] | |||
| 26 | 3-(1H-Pyrrol-3-yl)-propionamide | Drug Info | [14] | |||
| 27 | A-558693 | Drug Info | [10] | |||
| 28 | AW-00430 | Drug Info | [9] | |||
| 29 | Calpastatin | Drug Info | [15], [16] | |||
| 30 | DIHYDROXANTHOHUMOL | Drug Info | [9] | |||
| 31 | GNF-PF-4453 | Drug Info | [9] | |||
| 32 | mercaptoacrylate inhibitor of calpain 1 | Drug Info | [10] | |||
| 33 | N-(1-Benzyl-2-oxo-ethyl)-benzamide | Drug Info | [13] | |||
| 34 | PMID20690647C4b | Drug Info | [17] | |||
| 35 | PMID20690647C5a | Drug Info | [17] | |||
| 36 | PMID8831774C19 | Drug Info | [18] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Protein processing in endoplasmic reticulum | |||||
| 2 | Apoptosis | |||||
| 3 | Alzheimer's disease | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Degradation of the extracellular matrix | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Focal Adhesion | |||||
| 2 | Integrated Pancreatic Cancer Pathway | |||||
| 3 | Alzheimers Disease | |||||
| 4 | Integrin-mediated Cell Adhesion | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 2 | ClinicalTrials.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 3 | 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. (Ligand id: 2338). | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002441) | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007674) | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003692) | |||||
| REF 8 | An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31. | |||||
| REF 9 | 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. | |||||
| REF 10 | 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). | |||||
| REF 11 | Synthesis of a small library of diketopiperazines as potential inhibitors of calpain. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3034-8. | |||||
| REF 12 | 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. | |||||
| REF 13 | 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. | |||||
| REF 14 | Synthesis of cystamidin a (pyrrole-3-propanamide), a reported calpain inhibitor, Bioorg. Med. Chem. Lett. 6(13):1541-1542 (1996). | |||||
| REF 15 | Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Brain Res Rev. 2003 May;42(2):169-85. | |||||
| REF 16 | PEST sequences in the malaria parasite Plasmodium falciparum: a genomic study. Malar J. 2003 Jun 23;2:16. | |||||
| REF 17 | Peptidyl alpha-ketoamides with nucleobases, methylpiperazine, and dimethylaminoalkyl substituents as calpain inhibitors. J Med Chem. 2010 Sep 9;53(17):6326-36. | |||||
| REF 18 | Novel peptidyl alpha-keto amide inhibitors of calpains and other cysteine proteases. J Med Chem. 1996 Sep 27;39(20):4089-98. | |||||
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