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• W2036442353 abstract "Inhibition or allosteric modulation of mitogen-activated protein kinase kinases MEK1 and MEK2 (MEK1/2) represent a promising strategy for the discovery of new specific anticancer agents. In this paper, structure-based design, beginning from the lead compound PD98059, was used to study potential structural modifications on the chromone structure in order to obtain highly potent derivatives that target the allosteric pocket in MEK1. Subsequently, a small series of PD98059 analogs were synthesized to provide a first generation of chromone-based derivatives that inhibit the activation of MEK1 with IC50 values as low as 30 nM in vitro. Complementary cellular studies also showed that two of the compounds in the series inhibit the activity of MEK1/2 with IC50 values in the nanomolar range (73-97 nM). In addition, compounds in this series were found to inhibit the proliferation of a small panel of human cancer cell lines." @default.
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• W2036442353 date "2014-10-01" @default.
• W2036442353 modified "2023-10-14" @default.
• W2036442353 title "Towards the development of chromone-based MEK1/2 modulators" @default.
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• W2036442353 doi "https://doi.org/10.1016/j.ejmech.2014.07.018" @default.
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