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Discovery of a Novel Hsp90 Inhibitor by Fragment Linking
Author(s) -
Barker John J.,
Barker Oliver,
Courtney Stephen M.,
Gardiner Mihaly,
Hesterkamp Thomas,
Ichihara Osamu,
Mather Owen,
Montalbetti Christian A. G. N.,
Müller Annett,
Varasi Mario,
Whittaker Mark,
Yarnold Christopher J.
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000219
Subject(s) - fragment (logic) , hsp90 , hsp90 inhibitor , chemistry , computational biology , chaperone (clinical) , biology , biochemistry , heat shock protein , gene , computer science , medicine , algorithm , pathology
Hooking up! Hsp90 is a molecular chaperone involved in the stabilisation of numerous client proteins including those involved in oncogenic transformations. Through a high‐throughput biochemical fragment screen, we have identified novel fragment inhibitors of Hsp90. Two fragment hits were combined to give a dual‐fragment Hsp90 complex, and the following successful fragment‐linking resulted in a 1000‐fold improvement in activity.