Literature DB >> 24900504

Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors.

Hong Lin1, Mark J Schulz1, Ren Xie1, Jin Zeng1, Juan I Luengo1, Michael D Squire1, Rosanna Tedesco1, Junya Qu1, Karl Erhard1, James F Mack1, Kaushik Raha1, Ramona Plant1, Cynthia M Rominger1, Jennifer L Ariazi1, Christian S Sherk1, Michael D Schaber1, Jeanelle McSurdy-Freed1, Michael D Spengler1, Charles B Davis1, Mary Ann Hardwicke1, Ralph A Rivero1.   

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.

Entities:  

Keywords:  PI3K-beta inhibitor; PTEN-deficient; homology model; phosphatidylinositol 3-kinase; structure–activity relationship

Year:  2012        PMID： 24900504      PMCID： PMC4025772          DOI： 10.1021/ml300045b

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  11 in total

1.  A constitutively activated form of the p110beta isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice.

Authors:  Sang Hyun Lee; George Poulogiannis; Saumyadipta Pyne; Shidong Jia; Lihua Zou; Sabina Signoretti; Massimo Loda; Lewis Clayton Cantley; Thomas M Roberts
Journal:  Proc Natl Acad Sci U S A       Date:  2010-06-01       Impact factor: 11.205

2.  Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent β isoform selective phosphatidylinositol 3-kinase inhibitors.

Authors:  Robert M Sanchez; Karl Erhard; Mary Ann Hardwicke; Hong Lin; Jeanelle McSurdy-Freed; Ramona Plant; Kaushik Raha; Cynthia M Rominger; Michael D Schaber; Michael D Spengler; Michael L Moore; Hongyi Yu; Juan I Luengo; Rosanna Tedesco; Ralph A Rivero
Journal:  Bioorg Med Chem Lett       Date:  2012-03-16       Impact factor: 2.823

3.  Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor.

Authors:  Hong Xiang; Jeanelle McSurdy-Freed; Ganesh S Moorthy; Erin Hugger; Ramesh Bambal; Chao Han; Santiago Ferrer; Domingo Gargallo; Charles B Davis
Journal:  J Pharm Sci       Date:  2006-12       Impact factor: 3.534

4.  The role of PI 3-kinase p110beta in AKT signally, cell survival, and proliferation in human prostate cancer cells.

Authors:  Karen M Hill; Sara Kalifa; Jharna R Das; Tahira Bhatti; Martha Gay; Danielle Williams; Latonia Taliferro-Smith; Angelo M De Marzo
Journal:  Prostate       Date:  2010-05-15       Impact factor: 4.104

5.  Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors.

Authors:  Hong Lin; Karl Erhard; Mary Ann Hardwicke; Juan I Luengo; James F Mack; Jeanelle McSurdy-Freed; Ramona Plant; Kaushik Raha; Cynthia M Rominger; Robert M Sanchez; Michael D Schaber; Mark J Schulz; Michael D Spengler; Rosanna Tedesco; Ren Xie; Jin J Zeng; Ralph A Rivero
Journal:  Bioorg Med Chem Lett       Date:  2012-02-04       Impact factor: 2.823

6.  Nonradioactive methods for the assay of phosphoinositide 3-kinases and phosphoinositide phosphatases and selective detection of signaling lipids in cell and tissue extracts.

Authors:  Alexander Gray; Henric Olsson; Ian H Batty; Larisa Priganica; C Peter Downes
Journal:  Anal Biochem       Date:  2003-02-15       Impact factor: 3.365

7.  Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis.

Authors:  Shidong Jia; Zhenning Liu; Sen Zhang; Pixu Liu; Lei Zhang; Sang Hyun Lee; Jing Zhang; Sabina Signoretti; Massimo Loda; Thomas M Roberts; Jean J Zhao
Journal:  Nature       Date:  2008-06-25       Impact factor: 49.962

8.  PTEN-deficient cancers depend on PIK3CB.

Authors:  Susan Wee; Dmitri Wiederschain; Sauveur-Michel Maira; Alice Loo; Christine Miller; Rosalie deBeaumont; Frank Stegmeier; Yung-Mae Yao; Christoph Lengauer
Journal:  Proc Natl Acad Sci U S A       Date:  2008-08-28       Impact factor: 11.205

9.  Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent.

Authors:  Jing Ni; Qingsong Liu; Shaozhen Xie; Coby Carlson; Thanh Von; Kurt Vogel; Steve Riddle; Cyril Benes; Michael Eck; Thomas Roberts; Nathanael Gray; Jean Zhao
Journal:  Cancer Discov       Date:  2012-04-12       Impact factor: 39.397

10.  A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.

Authors:  Zachary A Knight; Beatriz Gonzalez; Morri E Feldman; Eli R Zunder; David D Goldenberg; Olusegun Williams; Robbie Loewith; David Stokoe; Andras Balla; Balazs Toth; Tamas Balla; William A Weiss; Roger L Williams; Kevan M Shokat
Journal:  Cell       Date:  2006-04-27       Impact factor: 41.582
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  5 in total

1.  [3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors.

Authors:  Hongyi Yu; Michael L Moore; Karl Erhard; Mary Ann Hardwicke; Hong Lin; Juan I Luengo; Jeanelle McSurdy-Freed; Ramona Plant; Junya Qu; Kaushik Raha; Cynthia M Rominger; Michael D Schaber; Michael D Spengler; Ralph A Rivero
Journal:  ACS Med Chem Lett       Date:  2013-01-10       Impact factor: 4.345

2.  L-Aminoacyl-triazine derivatives are isoform-selective PI3Kβ inhibitors that target non-conserved Asp862 of PI3Kβ

Authors:  Jo-Anne Pinson; Zhaohua Zheng; Michelle S Miller; David K Chalmers; Ian G Jennings; Philip E Thompson
Journal:  ACS Med Chem Lett       Date:  2013-02-14       Impact factor: 4.345

Review 3.  PI-3 kinase p110β: a therapeutic target in advanced prostate cancers.

Authors:  Benyi Li; Aijing Sun; Wencong Jiang; J Brantley Thrasher; Paul Terranova
Journal:  Am J Clin Exp Urol       Date:  2014-10-02

Review 4.  Recent syntheses of PI3K/Akt/mTOR signaling pathway inhibitors.

Authors:  Mark E Welker; George Kulik
Journal:  Bioorg Med Chem       Date:  2013-05-09       Impact factor: 3.641

Review 5.  Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents.

Authors:  Yu Liu; Wen-Zhu Wan; Yan Li; Guan-Lian Zhou; Xin-Guang Liu
Journal:  Oncotarget       Date:  2017-01-24
  5 in total

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