Literature DB >> 17451234

Identification of inhibitors of protein kinase B using fragment-based lead discovery.

Gordon Saxty, Steven J Woodhead, Valerio Berdini, Thomas G Davies, Marcel L Verdonk, Paul G Wyatt, Robert G Boyle, David Barford, Robert Downham, Michelle D Garrett, Robin A Carr.   

Abstract

Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80 microM) was identified as a novel, low molecular weight inhibitor of protein kinase B (PKB). Herein we describe the rapid elaboration of highly potent and ligand efficient analogues using a fragment growing approach. Iterative structure-based design was supported by protein-ligand structure determinations using a PKA-PKB "chimera" and a final protein-ligand structure of a lead compound in PKBbeta itself.

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Year:  2007        PMID： 17451234     DOI： 10.1021/jm070091b

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  23 in total

Review 1.  The rise of fragment-based drug discovery.

Authors:  Christopher W Murray; David C Rees
Journal:  Nat Chem       Date:  2009-06       Impact factor: 24.427

2.  Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics.

Authors:  Wan F Lau; Jane M Withka; David Hepworth; Thomas V Magee; Yuhua J Du; Gregory A Bakken; Michael D Miller; Zachary S Hendsch; Venkataraman Thanabal; Steve A Kolodziej; Li Xing; Qiyue Hu; Lakshmi S Narasimhan; Robert Love; Maura E Charlton; Samantha Hughes; Willem P van Hoorn; James E Mills
Journal:  J Comput Aided Mol Des       Date:  2011-05-21       Impact factor: 3.686

3.  Quantum mechanical pairwise decomposition analysis of protein kinase B inhibitors: validating a new tool for guiding drug design.

Authors:  Xiaohua Zhang; Alan C Gibbs; Charles H Reynolds; Martin B Peters; Lance M Westerhoff
Journal:  J Chem Inf Model       Date:  2010-04-26       Impact factor: 4.956

4.  Fragment-Based Discovery of Potent and Selective DDR1/2 Inhibitors.

Authors:  Christopher W Murray; Valerio Berdini; Ildiko M Buck; Maria E Carr; Anne Cleasby; Joseph E Coyle; Jayne E Curry; James E H Day; Phillip J Day; Keisha Hearn; Aman Iqbal; Lydia Y W Lee; Vanessa Martins; Paul N Mortenson; Joanne M Munck; Lee W Page; Sahil Patel; Susan Roomans; Kirsten Smith; Emiliano Tamanini; Gordon Saxty
Journal:  ACS Med Chem Lett       Date:  2015-06-04       Impact factor: 4.345

5.  Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.

Authors:  Christopher N Johnson; Valerio Berdini; Lijs Beke; Pascal Bonnet; Dirk Brehmer; Joseph E Coyle; Phillip J Day; Martyn Frederickson; Eddy J E Freyne; Ron A H J Gilissen; Christopher C F Hamlett; Steven Howard; Lieven Meerpoel; Rachel McMenamin; Sahil Patel; David C Rees; Andrew Sharff; François Sommen; Tongfei Wu; Joannes T M Linders
Journal:  ACS Med Chem Lett       Date:  2014-05-23       Impact factor: 4.345

6.  AT7867 is a potent and oral inhibitor of AKT and p70 S6 kinase that induces pharmacodynamic changes and inhibits human tumor xenograft growth.

Authors:  Kyla M Grimshaw; Lisa-Jane K Hunter; Timothy A Yap; Simon P Heaton; Mike I Walton; Steven J Woodhead; Lynsey Fazal; Matthias Reule; Thomas G Davies; Lisa C Seavers; Victoria Lock; John F Lyons; Neil T Thompson; Paul Workman; Michelle D Garrett
Journal:  Mol Cancer Ther       Date:  2010-04-27       Impact factor: 6.261

7.  Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant.

Authors:  Daoguang Zhang; Dongdong Tong; Dezhi Yang; Jing Sun; Fenghe Zhang; Guisen Zhao
Journal:  Medchemcomm       Date:  2018-07-03       Impact factor: 3.597

8.  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

Review 9.  Fragment-based approaches to enzyme inhibition.

Authors:  Alessio Ciulli; Chris Abell
Journal:  Curr Opin Biotechnol       Date:  2007-10-24       Impact factor: 9.740

10.  Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt).

Authors:  Tatiana McHardy; John J Caldwell; Kwai-Ming Cheung; Lisa J Hunter; Kevin Taylor; Martin Rowlands; Ruth Ruddle; Alan Henley; Alexis de Haven Brandon; Melanie Valenti; Thomas G Davies; Lynsey Fazal; Lisa Seavers; Florence I Raynaud; Suzanne A Eccles; G Wynne Aherne; Michelle D Garrett; Ian Collins
Journal:  J Med Chem       Date:  2010-03-11       Impact factor: 7.446
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