| Literature DB >> 24239008 |
Anna Rodina1, Pallav D Patel2, Yanlong Kang1, Yogita Patel3, Imad Baaklini3, Michael J H Wong3, Tony Taldone1, Pengrong Yan1, Chenghua Yang1, Ronnie Maharaj1, Alexander Gozman1, Maulik R Patel1, Hardik J Patel1, William Chirico4, Hediye Erdjument-Bromage5, Tanaji T Talele6, Jason C Young7, Gabriela Chiosis8.
Abstract
Hsp70s are important cancer chaperones that act upstream of Hsp90 and exhibit independent anti-apoptotic activities. To develop chemical tools for the study of human Hsp70, we developed a homology model that unveils a previously unknown allosteric site located in the nucleotide binding domain of Hsp70. Combining structure-based design and phenotypic testing, we discovered a previously unknown inhibitor of this site, YK5. In cancer cells, this compound is a potent and selective binder of the cytosolic but not the organellar human Hsp70s and has biological activity partly by interfering with the formation of active oncogenic Hsp70/Hsp90/client protein complexes. YK5 is a small molecule inhibitor rationally designed to interact with an allosteric pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70.Entities:
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Year: 2013 PMID： 24239008 PMCID： PMC3985611 DOI： 10.1016/j.chembiol.2013.10.008
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521