TY - JOUR
T1 - Discovery of a novel Hsp90 inhibitor by fragment linking
AU - Barker, John J.
AU - Barker, Oliver
AU - Courtney, Stephen M.
AU - Gardiner, Mihaly
AU - Hesterkamp, Thomas
AU - Ichihara, Osamu
AU - Mather, Owen
AU - Montalbetti, Christian A G N
AU - Müller, Annett
AU - Varasi, Mario
AU - Whittaker, Mark
AU - Yarnold, Christopher J.
PY - 2010/10/4
Y1 - 2010/10/4
N2 - 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. (Chemical Equation Presented).
AB - 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. (Chemical Equation Presented).
KW - Fragment linking
KW - Fragment-based screening
KW - Heat shock protein 90
KW - Hsp90
KW - Structure-based drug design
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U2 - 10.1002/cmdc.201000219
DO - 10.1002/cmdc.201000219
M3 - Article
C2 - 20665758
AN - SCOPUS:77957655200
VL - 5
SP - 1697
EP - 1700
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 10
ER -