【摘 要】
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The phosphatidylinositol 3-kinase (PI3K) pathway is involved in many cellular functions including cell growth,metabolism,and transformation.Hyperactivation of t
【机 构】
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The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Ins
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The phosphatidylinositol 3-kinase (PI3K) pathway is involved in many cellular functions including cell growth,metabolism,and transformation.Hyperactivation of this pathway contributes to tumorigenesis,therefore,PI3K is a major target for anticancer drug discovery.Since the PI3Kα isoform is implicated mostly in cancer,we conducted a high-throughput screening (HTS) campaign using a 3-step PI3K homogenous time-resolved fluorescence assay against this isoform bearing the H1047R mutation.A total of 288,000 synthetic and natural product-derived compounds were screened and of which,we identified 124 initial hits that were further selected by considering the predicted binding mode,relationship to known pan-assay interference compounds and previous descriptions as a lipid kinase inhibitor.A total of 24 compounds were then tested for concentration-dependent responses.These hit compounds provide novel scaffolds that can potentially be optimized to create novel PI3K inhibitors.
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