Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)

[Image: see text] In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encode...

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Detalles Bibliográficos
Autores principales: Yang, Hongfang, Medeiros, Patricia F., Raha, Kaushik, Elkins, Patricia, Lind, Kenneth E., Lehr, Ruth, Adams, Nicholas D., Burgess, Joelle L., Schmidt, Stanley J., Knight, Steven D., Auger, Kurt R., Schaber, Michael D., Franklin, G. Joseph, Ding, Yun, DeLorey, Jennifer L., Centrella, Paolo A., Mataruse, Sibongile, Skinner, Steven R., Clark, Matthew A., Cuozzo, John W., Evindar, Ghotas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434457/
https://www.ncbi.nlm.nih.gov/pubmed/26005528
http://dx.doi.org/10.1021/acsmedchemlett.5b00025
Descripción
Sumario:[Image: see text] In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.

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