Phosphorylation of the Wnt receptor LRP6 directly inhibits glycogen synthase kinase-3 by acting as a pseudosubstrate that stabilizes an active conformation of the enzyme, identical to autoinhibition by phosphorylation of its N terminus.
MARCH5 mediates a pathway driving MCL1 degradation in response to cellular stress, which sensitizes to BH3 mimetic drugs targeting BCLXL and provides a broadly effective therapeutic strategy for solid tumors.
Anti-targets are proteins that cause problems when inhibited along with an intended target and our novel chemical strategy affords unprecedented selectivity in the context of FLT3 vs. KIT inhibition for treatment of a devastating blood cancer.
A geneome-scale shRNA screen identifies five genes whose suppression promotes cell death upon PI3K inhibition both in vitro and in vivo, thus suggesting potential combination therapies involving PI3K inhibition.