title: Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors.
abstract: A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been identified. This chemotype has provided an excellent tool compound, 18, that showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage-independent conditions, and it also demonstrated pharmacodynamic effects and efficacy in a PTEN-deficient prostate cancer PC-3 xenograft mouse model.
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schulz
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Ren
authors.initials: R
authors.lastname: Xie
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Luengo
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Squire
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tedesco
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Junya
authors.initials: J
authors.lastname: Qu
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Karl
authors.initials: K
authors.lastname: Erhard
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Mack
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Raha
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Ramona
authors.initials: R
authors.lastname: Plant
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Rominger
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ariazi
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Sherk
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schaber
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: McSurdy-Freed
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Spengler
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Davis
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hardwicke
authors.affiliation: Cancer Metabolism Chemistry; Cancer Metabolism Biology; Cancer Metabolism DMPK; Platform Technology Sciences-Computational Chemistry; and Platform Technology Sciences-Screening & Compound Profiling; GlaxoSmithKline , 1250 South Collegeville Road, Collegeville, Pennsylvania 19426-0989, United States.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Rivero
keywords: PI3K-beta inhibitor; PTEN-deficient; homology model; phosphatidylinositol 3-kinase; structure–activity relationship