1vyz
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:N5b+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:N5b+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=N5B:N-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)BENZAMIDE'>N5B</scene> | |LIGAND= <scene name='pdbligand=N5B:N-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)BENZAMIDE'>N5B</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/ | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vyz OCA], [http://www.ebi.ac.uk/pdbsum/1vyz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vyz RCSB]</span> | ||
}} | }} | ||
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3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding., Pevarello P, Brasca MG, Amici R, Orsini P, Traquandi G, Corti L, Piutti C, Sansonna P, Villa M, Pierce BS, Pulici M, Giordano P, Martina K, Fritzen EL, Nugent RA, Casale E, Cameron A, Ciomei M, Roletto F, Isacchi A, Fogliatto G, Pesenti E, Pastori W, Marsiglio A, Leach KL, Clare PM, Fiorentini F, Varasi M, Vulpetti A, Warpehoski MA, J Med Chem. 2004 Jun 17;47(13):3367-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15189033 15189033] | 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding., Pevarello P, Brasca MG, Amici R, Orsini P, Traquandi G, Corti L, Piutti C, Sansonna P, Villa M, Pierce BS, Pulici M, Giordano P, Martina K, Fritzen EL, Nugent RA, Casale E, Cameron A, Ciomei M, Roletto F, Isacchi A, Fogliatto G, Pesenti E, Pastori W, Marsiglio A, Leach KL, Clare PM, Fiorentini F, Varasi M, Vulpetti A, Warpehoski MA, J Med Chem. 2004 Jun 17;47(13):3367-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15189033 15189033] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 2 7.11 1]] | ||
[[Category: Amici, R.]] | [[Category: Amici, R.]] | ||
[[Category: Brasca, M G.]] | [[Category: Brasca, M G.]] | ||
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[[Category: Vulpetti, A.]] | [[Category: Vulpetti, A.]] | ||
[[Category: Warpehoski, M A.]] | [[Category: Warpehoski, M A.]] | ||
| - | [[Category: N5B]] | ||
[[Category: cell division]] | [[Category: cell division]] | ||
[[Category: cyclin]] | [[Category: cyclin]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:28:56 2008'' |
Revision as of 21:28, 30 March 2008
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| , resolution 2.21Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF CDK2 COMPLEXED WITH PNU-181227
Overview
Abnormal proliferation mediated by disruption of the normal cell cycle mechanisms is a hallmark of virtually all cancer cells. Compounds targeting complexes between cyclin-dependent kinases (CDK) and cyclins, such as CDK2/cyclin A and CDK2/cyclin E, and inhibiting their kinase activity are regarded as promising antitumor agents to complement the existing therapies. From a high-throughput screening effort, we identified a new class of CDK2/cyclin A/E inhibitors. The hit-to-lead expansion of this class is described. X-ray crystallographic data of early compounds in this series, as well as in vitro testing funneled for rapidly achieving in vivo efficacy, led to a nanomolar inhibitor of CDK2/cyclin A (N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(2-naphthyl)acetamide (41), PNU-292137, IC50 = 37 nM) with in vivo antitumor activity (TGI > 50%) in a mouse xenograft model at a dose devoid of toxic effects.
About this Structure
1VYZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding., Pevarello P, Brasca MG, Amici R, Orsini P, Traquandi G, Corti L, Piutti C, Sansonna P, Villa M, Pierce BS, Pulici M, Giordano P, Martina K, Fritzen EL, Nugent RA, Casale E, Cameron A, Ciomei M, Roletto F, Isacchi A, Fogliatto G, Pesenti E, Pastori W, Marsiglio A, Leach KL, Clare PM, Fiorentini F, Varasi M, Vulpetti A, Warpehoski MA, J Med Chem. 2004 Jun 17;47(13):3367-80. PMID:15189033
Page seeded by OCA on Mon Mar 31 00:28:56 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Amici, R. | Brasca, M G. | Cameron, A. | Casale, E. | Ciomei, M. | Clare, P M. | Corti, L. | Fiorentini, F. | Fogliatto, G. | Giordano, G. | Isacchi, A. | Leach, K L. | Lfritzen, E. | Marsiglio, W. | Martina, K. | Nugent, R A. | Orsini, P. | Pastori, W. | Pesenti, E. | Pevarello, P. | Pierce, B S. | Piutti, C. | Pulici, M. | Roletto, F. | Sansonna, P. | Traquandi, G. | Varasi, M. | Villa, M. | Vulpetti, A. | Warpehoski, M A. | Cell division | Cyclin | Phosphorylation | Protein kinase | Serine/threonine-protein kinase | Transferase
