1oi9

File:1oi9.gif

spinqualitylabelsall models 1oi9, resolution 2.100Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR

OverviewOverview

The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase, inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as, the lead in a structure-based drug discovery program resulting in the, discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM, and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). The SAR for, this series have been explored further by the synthesis and evaluation of, 45 N(2)-substituted analogues of NU2058. These studies have confirmed the, requirement for the hydrogen bonding N(2)-NH group and the requirement for, an aromatic N(2)-substituent to confer potency in the series. Additional, potency is conferred by the presence of a group capable of donating a, hydrogen bond at the 4'-position, for example, the 4'-hydroxy ... [(full description)]

About this StructureAbout this Structure

1OI9 is a [Protein complex] structure of sequences from [Homo sapiens] with MG, N20 and SGM as [ligands]. Active as [Transferred entry: 2.7.11.1], with EC number [2.7.1.37]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

ReferenceReference

N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2., Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ, J Med Chem. 2004 Jul 15;47(15):3710-22. PMID:15239650

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