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Gray NS, et al.  (1998) Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 281(5376):533-8

Abstract: Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2-cyclin A kinase complex and of Saccharomyces cerevisiae Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex. The cellular effects of these compounds were characterized in mammalian cells and yeast. In the latter case the effects were characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays. Purine libraries could provide useful tools for analyzing a variety of signaling and regulatory pathways and may lead to the development of new therapeutics.

Status: Published Type: Journal Article PubMed ID: 9677190

Topics addressed in this paper

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ACH1 ATR1 BDH2 CAK1 CDC28 CLB1 CLB2 CTS1 CTT1 CYC3
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Genomic expression study yg ball
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Topics Genes linked to topics (#11 - 20 )
DSE2 EGT2 FAR1 GPG1 GPH1 GSC2 HAC1 HAP4 HBT1 HSP104
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Topics Genes linked to topics (#21 - 30 )
HSP12 HSP26 HSP30 HSP42 HSP82 HTA2 HTB2 HXT5 ILV6 KIN28
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Topics Genes linked to topics (#31 - 40 )
NQM1 NRM1 PCK1 PCL5 PDR10 PDR15 PGM2 PHM6 PHM8 PHO5
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Topics Genes linked to topics (#41 - 50 )
PHO8 PHO80 PHO81 PHO84 PHO85 PHO89 RSF2 RTC2 SDS24 SPI1
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Topics Genes linked to topics (#51 - 58 )
SSE2 SSN3 TFS1 TOS3 UBI4 YKL071W YLR311C YOR248W
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