Literature DB >> 21621413

Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability.

Qingsong Liu1, Jinhua Wang, Seong A Kang, Carson C Thoreen, Wooyoung Hur, Hwan Geun Choi, David L Waller, Taebo Sim, David M Sabatini, Nathanael S Gray.   

Abstract

Starting from small molecule mTOR inhibitor Torin1, replacement of the piperazine ring with a phenyl ring resulted in a new series of mTOR inhibitors (as exemplified by 10) that showed superior potency and selectivity for mTOR, along with significantly improved mouse liver microsome stability and a longer in vivo half-life.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 21621413      PMCID： PMC3929239          DOI： 10.1016/j.bmcl.2011.04.129

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  21 in total

1.  The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase.

Authors:  Karine Malagu; Heather Duggan; Keith Menear; Marc Hummersone; Sylvie Gomez; Christine Bailey; Peter Edwards; Jan Drzewiecki; Frédéric Leroux; Mar Jimenez Quesada; Gesine Hermann; Stephanie Maine; Carrie-Anne Molyneaux; Armelle Le Gall; James Pullen; Ian Hickson; Lisa Smith; Sharon Maguire; Niall Martin; Graeme Smith; Martin Pass
Journal:  Bioorg Med Chem Lett       Date:  2009-08-13       Impact factor: 2.823

2.  Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: discovery of highly potent and selective analogs with improved human microsomal stability.

Authors:  David J Richard; Jeroen C Verheijen; Kevin Curran; Joshua Kaplan; Lourdes Toral-Barza; Irwin Hollander; Judy Lucas; Ker Yu; Arie Zask
Journal:  Bioorg Med Chem Lett       Date:  2009-10-25       Impact factor: 2.823

3.  mTOR Mediated Anti-Cancer Drug Discovery.

Authors:  Qingsong Liu; Carson Thoreen; Jinhua Wang; David Sabatini; Nathanael S Gray
Journal:  Drug Discov Today Ther Strateg       Date:  2009

4.  AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.

Authors:  Christine M Chresta; Barry R Davies; Ian Hickson; Tom Harding; Sabina Cosulich; Susan E Critchlow; John P Vincent; Rebecca Ellston; Darren Jones; Patrizia Sini; Dominic James; Zoe Howard; Phillippa Dudley; Gareth Hughes; Lisa Smith; Sharon Maguire; Marc Hummersone; Karine Malagu; Keith Menear; Richard Jenkins; Matt Jacobsen; Graeme C M Smith; Sylvie Guichard; Martin Pass
Journal:  Cancer Res       Date:  2009-12-22       Impact factor: 12.701

5.  Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.

Authors:  Dos D Sarbassov; Siraj M Ali; Shomit Sengupta; Joon-Ho Sheen; Peggy P Hsu; Alex F Bagley; Andrew L Markhard; David M Sabatini
Journal:  Mol Cell       Date:  2006-04-06       Impact factor: 17.970

Review 6.  Targeting the phosphoinositide 3-kinase pathway in cancer.

Authors:  Pixu Liu; Hailing Cheng; Thomas M Roberts; Jean J Zhao
Journal:  Nat Rev Drug Discov       Date:  2009-08       Impact factor: 84.694

7.  Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2.

Authors:  Ker Yu; Celine Shi; Lourdes Toral-Barza; Judy Lucas; Boris Shor; Jae Eun Kim; Wei-Guo Zhang; Robert Mahoney; Christine Gaydos; Luanna Tardio; Sung Kyoo Kim; Roger Conant; Kevin Curran; Joshua Kaplan; Jeroen Verheijen; Semiramis Ayral-Kaloustian; Tarek S Mansour; Robert T Abraham; Arie Zask; James J Gibbons
Journal:  Cancer Res       Date:  2010-01-12       Impact factor: 12.701

8.  Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin.

Authors:  Ker Yu; Lourdes Toral-Barza; Celine Shi; Wei-Guo Zhang; Judy Lucas; Boris Shor; Jamie Kim; Jeroen Verheijen; Kevin Curran; David J Malwitz; Derek C Cole; John Ellingboe; Semiramis Ayral-Kaloustian; Tarek S Mansour; James J Gibbons; Robert T Abraham; Pawel Nowak; Arie Zask
Journal:  Cancer Res       Date:  2009-07-07       Impact factor: 12.701

9.  An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1.

Authors:  Carson C Thoreen; Seong A Kang; Jae Won Chang; Qingsong Liu; Jianming Zhang; Yi Gao; Laurie J Reichling; Taebo Sim; David M Sabatini; Nathanael S Gray
Journal:  J Biol Chem       Date:  2009-01-15       Impact factor: 5.157

10.  Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR).

Authors:  Juan M García-Martínez; Jennifer Moran; Rosemary G Clarke; Alex Gray; Sabina C Cosulich; Christine M Chresta; Dario R Alessi
Journal:  Biochem J       Date:  2009-06-12       Impact factor: 3.857
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  5 in total

1.  Effects of Metformin and a Mammalian Target of Rapamycin (mTOR) ATP-Competitive Inhibitor on Targeted Metabolomics in Pancreatic Cancer Cell Line.

Authors:  Ghada A Soliman; Sharalyn M Steenson; Asserewou H Etekpo
Journal:  Metabolomics (Los Angel)       Date:  2016-08-20

Review 2.  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

3.  Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and Evaluation of their Plasmodium falciparum Gametocytocidal Activities.

Authors:  Hao Li; Wei Sun; Xiuli Huang; Xiao Lu; Paresma R Patel; Myunghoon Kim; Meghan J Orr; Richard M Fisher; Takeshi Q Tanaka; John C McKew; Anton Simeonov; Philip E Sanderson; Wei Zheng; Kim C Williamson; Wenwei Huang
Journal:  ACS Comb Sci       Date:  2017-10-27       Impact factor: 3.784

Review 4.  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.  The potential role of nanotechnology in therapeutic approaches for triple negative breast cancer.

Authors:  Rebecca Johnson; Nirupama Sabnis; Walter J McConathy; Andras G Lacko
Journal:  Pharmaceutics       Date:  2013       Impact factor: 6.321
  5 in total

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