Literature DB >> 21459573

Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.

Daniel A Erlanson1, Joseph W Arndt, Mark T Cancilla, Kathy Cao, Robert A Elling, Nicki English, Jessica Friedman, Stig K Hansen, Cathy Hession, Ingrid Joseph, Gnanasambandam Kumaravel, Wen-Cherng Lee, Ken E Lind, Robert S McDowell, Konrad Miatkowski, Christine Nguyen, Thinh B Nguyen, Sophia Park, Nuzhat Pathan, David M Penny, Michael J Romanowski, Daniel Scott, Laura Silvian, Robert L Simmons, Bradley T Tangonan, Wenjin Yang, Lihong Sun.   

Abstract

We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.
Copyright © 2011 Elsevier Ltd. All rights reserved.

Entities:  

Mesh：

Substances：

Year:  2011        PMID： 21459573     DOI： 10.1016/j.bmcl.2011.03.032

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


  16 in total

Review 1.  Systems pharmacology: network analysis to identify multiscale mechanisms of drug action.

Authors:  Shan Zhao; Ravi Iyengar
Journal:  Annu Rev Pharmacol Toxicol       Date:  2012       Impact factor: 13.820

2.  Novel isoquinolone PDK1 inhibitors discovered through fragment-based lead discovery.

Authors:  M Catherine Johnson; Qiyue Hu; Laura Lingardo; Rose Ann Ferre; Samantha Greasley; Jiangli Yan; John Kath; Ping Chen; Jacques Ermolieff; Gordon Alton
Journal:  J Comput Aided Mol Des       Date:  2011-07-22       Impact factor: 3.686

3.  Protein-Protein Interactions as New Targets for Ion Channel Drug Discovery.

Authors:  Svetla Stoilova-McPhie; Syed Ali; Fernanda Laezza
Journal:  Austin J Pharmacol Ther       Date:  2013-12-31

Review 4.  Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery.

Authors:  Kenneth K Hallenbeck; David M Turner; Adam R Renslo; Michelle R Arkin
Journal:  Curr Top Med Chem       Date:  2017       Impact factor: 3.295

Review 5.  PDK1 inhibitors.

Authors:  Elisa Barile; Surya K De; Maurizio Pellecchia
Journal:  Pharm Pat Anal       Date:  2012-05

6.  Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

Authors:  Elinor Meiby; Stefan Knapp; Jonathan M Elkins; Sten Ohlson
Journal:  Anal Bioanal Chem       Date:  2012-08-24       Impact factor: 4.142

7.  Galactose-1 phosphate uridylyltransferase (GalT) gene: A novel positive regulator of the PI3K/Akt signaling pathway in mouse fibroblasts.

Authors:  Bijina Balakrishnan; Wyman Chen; Manshu Tang; Xiaoping Huang; Didem Demirbas Cakici; Anwer Siddiqi; Gerard Berry; Kent Lai
Journal:  Biochem Biophys Res Commun       Date:  2016-01-08       Impact factor: 3.575

Review 8.  The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1.

Authors:  Xinyuan Xu; Yingyi Chen; Qiang Fu; Duan Ni; Jian Zhang; Xiaolong Li; Shaoyong Lu
Journal:  J Enzyme Inhib Med Chem       Date:  2019-12       Impact factor: 5.051

Review 9.  Mitochondrial Ca2+ Signaling in Health, Disease and Therapy.

Authors:  Lorenzo Modesti; Alberto Danese; Veronica Angela Maria Vitto; Daniela Ramaccini; Gianluca Aguiari; Roberta Gafà; Giovanni Lanza; Carlotta Giorgi; Paolo Pinton
Journal:  Cells       Date:  2021-05-25       Impact factor: 6.600

Review 10.  Exploration of type II binding mode: A privileged approach for kinase inhibitor focused drug discovery?

Authors:  Zheng Zhao; Hong Wu; Li Wang; Yi Liu; Stefan Knapp; Qingsong Liu; Nathanael S Gray
Journal:  ACS Chem Biol       Date:  2014-04-29       Impact factor: 5.100
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.