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.
In keratinocytes, the BRAF and RAF1 proteins work independently to balance the activity of mitogenic and stress kinase cascades and uphold the mechanical and immunological barrier functions of the epidermis.
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.
Fibrolamellar carcinoma results from a genetic lesion that produces the DNAJ-PKAc fusion kinase, which is recruited into macromolecular complexes and is sensitive to combinations of signal transduction inhibitor drugs.