Integration of ligand and structure-based virtual screening for the identification of the first dual targeting agent for heat shock protein 90 (Hsp90) and tubulin.
We describe the discovery of a novel indazole-based scaffold that represents the "first-in-class" dual Hsp90/tubulin binding compound. Individual known ligands for both targets shared similar 3',4',5'-trimethoxyphenyl cores, and from this it was hypothesized that application of an integrated ligand and structure-based virtual screening (VS) workflow could yield a single scaffold with dual binding affinity. Following validation of the VS protocol, we successfully identified a novel dual inhibitor, sourced from a commercial screening collection of 160 000 compounds.
Knox
Andrew J S
AJ
Molecular Design Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Price
Trevor
T
Pawlak
Michal
M
Golfis
Georgia
G
Flood
Christopher T
CT
Fayne
Darren
D
Williams
D Clive
DC
Meegan
Mary J
MJ
Lloyd
David G
DG