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Discovery of a Potent Class of PI3K? Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).

ABSTRACT: In the search of PI3K p110? 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 p110? protein.

SUBMITTER: Yang H

PROVIDER: S-EPMC4434457 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Yang Hongfang H Medeiros Patricia F PF Raha Kaushik K Elkins Patricia P Lind Kenneth E KE Lehr Ruth R Adams Nicholas D ND Burgess Joelle L JL Schmidt Stanley J SJ Knight Steven D SD Auger Kurt R KR Schaber Michael D MD Franklin G Joseph GJ Ding Yun Y DeLorey Jennifer L JL Centrella Paolo A PA Mataruse Sibongile S Skinner Steven R SR Clark Matthew A MA Cuozzo John W JW Evindar Ghotas G

ACS medicinal chemistry letters 20150320 5

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. ...[more]

PMID: 26005528

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