2 research outputs found
Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)
In the search of PI3K p110α
wild type and H1047R mutant selective small molecule leads, an encoded
library technology (ELT) campaign against the desired target proteins
was performed which led to the discovery of a selective chemotype
for PI3K isoforms from a three-cycle DNA encoded library. An X-ray
crystal structure of a representative inhibitor from this chemotype
demonstrated a unique binding mode in the p110α protein
Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2
The histone H3-lysine 27 (H3K27) methyltransferase EZH2
plays a
critical role in regulating gene expression, and its aberrant activity
is linked to the onset and progression of cancer. As part of a drug
discovery program targeting EZH2, we have identified highly potent,
selective, SAM-competitive, and cell-active EZH2 inhibitors, including
GSK926 (<b>3</b>) and GSK343 (<b>6</b>). These compounds
are small molecule chemical tools that would be useful to further explore the biology of EZH2