National Center for
2UW3: Structure Of Pka-Pkb Chimera Complexed With 5-Methyl-4- Phenyl-1h-Pyrazole
J. Med. Chem. (2007) 50 p.2293-2296
Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80 microM) was identified as a novel, low molecular weight inhibitor of protein kinase B (PKB). Herein we describe the rapid elaboration of highly potent and ligand efficient analogues using a fragment growing approach. Iterative structure-based design was supported by protein-ligand structure determinations using a PKA-PKB "chimera" and a final protein-ligand structure of a lead compound in PKBbeta itself.