2528 Identification of Dual Specificity Phosphatase... -
[Cached Version]
Published on: 12/1/2001
Last Visited: 12/9/2002
Andreas Vogt, Michael G. Tarpley, Kathleen A. Cooley, Peter Wipf, and John S. Lazo University of Pittsburgh
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Presenting author: Andreas Vogt, University of Pittsburgh, USA
Few cell-active inhibitors of the oncogenic cell-cycle phosphatase Cdc25 have been described.To assess the utility of a cell-based assay as a primary drug discovery screen, we have evaluated 1991 compounds in the NCI DiverSet for phospho-Erk accumulation in intact cells.The assay yielded an initial hit rate of 1.7% (34 compounds).Ten of these (0.5%) were confirmed by microscopic examination.Of the 10 verified hits, six (60%) inhibited Cdc25B in vitro by more than 50%.Four compounds inhibited Cdc25B by over 80%, and none inhibited VHR or PTP1B.A focused library with submicromolar in vitro Cdc25 inhibitory activity containing 22 agents from the NCI repository and 14 synthetic analogs showed a substantial enrichment for phospho-Erk accumulators (7 out of 36 or 19.5%) compared with the parent NCI library.