Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor.

@article{Gonzlez2012IdentificationOE,
  title={Identification of ETP-46321, a potent and orally bioavailable PI3K $\alpha$, $\delta$ inhibitor.},
  author={S. Mart{\'i}nez Gonz{\'a}lez and Ana-Isabel Hern{\'a}ndez and Carmen Varela and Sonsoles Rodr{\'i}guez-Ar{\'i}stegui and Milagros Lorenzo and Antonio Rodr{\'i}guez and Virginia Rivero and J. I. Mart{\'i}n and Carl Gustav Saluste and Francisco J. Ramos-Lima and Elena Cend{\'o}n and D. Cebri{\'a}n and Enara Aguirre and E. G{\'o}mez-Casero and M. Albarr{\'a}n and P. Alfonso and Beatriz Garc{\'i}a-Serelde and J. Oyarz{\'a}bal and O. Rabal and F. Mulero and Teresa Gonzalez-Granda and W. Link and J. Fominaya and M. Barbacid and J. Bischoff and P. Pizcueta and J. Pastor},
  journal={Bioorganic \& medicinal chemistry letters},
  year={2012},
  volume={22 10},
  pages={
          3460-6
        }
}
Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein, we describe the optimization of imidazo [1,2-a] pyrazines, which allow us to identify compound 14 (ETP-46321), with potent biochemical and cellular activity and good pharmacokinetic properties (PK) after oral dosing. ETP-46321 PK/PD studies showed time dependent downregulation of AKT(Ser473) phosphorylation, which… Expand
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Identification of novel PI3K inhibitors through a scaffold hopping strategy.
ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis.
Recent syntheses of PI3K/Akt/mTOR signaling pathway inhibitors.
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