Cell-Penetrating Bisubstrate-Based Protein Kinase C Inhibitors
ACS Chem. Biol., Article ASAP
This article tries to tackle the kinase selectivity problem through a bivalent approach that targets the adenosine pocket and a substrate binding groove with one ligand. Bivalent inhibitors have been around for a while, but their main problem is lack of cell permeability. The authors in this paper address this issue by using cell-penetrating peptides (CPP) in an effort to target PKC. Looks like they got single-digit micromolar inhibition and good selectivity, plus cell permeability.
