Literature DB >> 21420856

Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA.

Rui Xu1, Anna Banka, James F Blake, Ian S Mitchell, Eli M Wallace, Josef R Bencsik, Nicholas C Kallan, Keith L Spencer, Susan L Gloor, Matthew Martinson, Tyler Risom, Stefan D Gross, Tony H Morales, Wen-I Wu, Guy P A Vigers, Barbara J Brandhuber, Nicholas J Skelton.   

Abstract

We describe the design and synthesis of novel bicyclic spiro sulfonamides as potent Akt inhibitors. Through structure-based rational design, we have successfully improved PKA selectivity of previously disclosed spirochromanes. Representative compounds showed favorable Akt potency while exhibiting up to 1000-fold selectivity against PKA.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 21420856     DOI： 10.1016/j.bmcl.2011.02.098

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


  6 in total

Review 1.  Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape.

Authors:  Margrith E Mattmann; Sydney L Stoops; Craig W Lindsley
Journal:  Expert Opin Ther Pat       Date:  2011-06-02       Impact factor: 6.674

2.  Combining ligand- and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1.

Authors:  Priya Mahajan; Bhumika Wadhwa; Manas Ranjan Barik; Fayaz Malik; Amit Nargotra
Journal:  Mol Divers       Date:  2019-02-23       Impact factor: 2.943

3.  Binding selectivity studies of PKBα using molecular dynamics simulation and free energy calculations.

Authors:  Shi-Feng Chen; Yang Cao; Jiong-Jiong Chen; Jian-Zhong Chen
Journal:  J Mol Model       Date:  2013-10-02       Impact factor: 1.810

4.  Efficient and cost effective production of active-form human PKB using silkworm larvae.

Authors:  Ryoko Maesaki; Ryosuke Satoh; Masato Taoka; Teppei Kanaba; Tsunaki Asano; Chiharu Fujita; Toshinobu Fujiwara; Yutaka Ito; Toshiaki Isobe; Toshio Hakoshima; Katsumi Maenaka; Masaki Mishima
Journal:  Sci Rep       Date:  2014-08-15       Impact factor: 4.379

Review 5.  Drug Discovery of Plausible Lead Natural Compounds That Target the Insulin Signaling Pathway: Bioinformatics Approaches.

Authors:  Siba Shanak; Najlaa Bassalat; Ahmad Barghash; Sleman Kadan; Mahmoud Ardah; Hilal Zaid
Journal:  Evid Based Complement Alternat Med       Date:  2022-03-20       Impact factor: 2.629

6.  Pharmacophore modeling, virtual screening, and molecular docking studies for discovery of novel Akt2 inhibitors.

Authors:  Jia Fei; Lu Zhou; Tao Liu; Xiang-Yang Tang
Journal:  Int J Med Sci       Date:  2013-01-23       Impact factor: 3.738
  6 in total

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