Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK
作者： A. V. Galkin , J. S. Melnick , S. Kim , T. L. Hood , N. Li
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摘要: Constitutive overexpression and activation of NPM-ALK fusion protein [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival proliferation anaplastic large-cell lymphomas (ALCLs). We have identified highly potent selective small-molecule ALK inhibitor, NVP-TAE684, which blocked growth ALCL-derived ALK-dependent cell lines with IC50 values between 2 10 nM. NVP-TAE684 treatment resulted in rapid sustained inhibition phosphorylation its downstream effectors subsequent induction apoptosis cycle arrest. In vivo, suppressed lymphomagenesis two independent models ALK-positive ALCL induced regression established Karpas-299 lymphomas. also down-regulation CD30 expression, suggesting may be used as biomarker therapeutic kinase activity inhibition.
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