1vyw: Difference between revisions

Revision as of 11:17, 3 February 2008

STRUCTURE OF CDK2/CYCLIN A WITH PNU-292137

OverviewOverview

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 StructureAbout this Structure

1VYW is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

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 Sun Feb 3 10:17:20 2008

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OCA

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-[[Image:1vyw.jpg|left|200px]]<br /><applet load="1vyw" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1vyw.jpg|left|200px]]<br /><applet load="1vyw" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1vyw, resolution 2.30&Aring;" />
 '''STRUCTURE OF CDK2/CYCLIN A WITH PNU-292137'''<br />
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 ==About this Structure==
-VYW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and 292 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Known structural/functional Site: <scene name='pdbsite=DG1:So4 Binding Site For Chain D'>DG1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VYW OCA].
+VYW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=292:'>292</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Known structural/functional Site: <scene name='pdbsite=DG1:So4+Binding+Site+For+Chain+D'>DG1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VYW OCA].
 ==Reference==
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 [[Category: transferase]]
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