title: Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).
abstract: 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.
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Yang
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Medeiros
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Raha
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Patricia
authors.initials: P
authors.lastname: Elkins
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Lind
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehr
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Adams
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Joelle L
authors.initials: JL
authors.lastname: Burgess
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Schmidt
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Knight
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Auger
authors.affiliation: Computational and Structural Chemistry, Platform Technology and Science, Biological Reagents and Assay Development, Platform Technology and Science, Oncology Research, and Screening and Compound Profiling, Platform Technology and Science, GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schaber
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: G Joseph
authors.initials: GJ
authors.lastname: Franklin
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: DeLorey
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Centrella
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Mataruse
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Skinner
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Clark
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Cuozzo
authors.affiliation: MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
authors.forename: Ghotas
authors.initials: G
authors.lastname: Evindar
keywords: ELT; Encoded Library technology; PI3K p110α (H1047R); PI3Kα; p110α