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

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

  • Bioorg Med Chem Lett. 2012 May 15;22(10):3460-6. doi: 10.1016/j.bmcl.2012.03.090.
Sonia Martínez González 1,  Ana Isabel Hernández,  Carmen Varela,  Sonsoles Rodríguez-Arístegui,  Milagros Lorenzo,  Antonio Rodríguez,  Virginia Rivero,  José Ignacio Martín,  Carl Gustav Saluste,  Francisco Ramos-Lima,  Elena Cendón,  David Cebrián,  Enara Aguirre,  Elena Gomez-Casero,  Maribel Albarrán,  Patricia Alfonso,  Beatriz García-Serelde,  Julen Oyarzabal,  Obdulia Rabal,  Francisca Mulero,  Teresa Gonzalez-Granda,  Wolfgang Link,  Jesús Fominaya,  Mariano Barbacid,  James R Bischoff,  Pilar Pizcueta,  Joaquín Pastor
Affiliations

Affiliation

  • 1 Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
PMID: 22520259 DOI: 10.1016/j.bmcl.2012.03.090
Abstract

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 correlates with compound levels in tumor tissue and demonstrating to be efficacious in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation. Treatment with ETP-46321 resulted in significant tumor growth inhibition.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12340
    99.65%, PI3K Inhibitor