Allosteric Inhibition Via Nonpolar Terpenoid Inhibitors.

Protein tyrosine phosphatases (PTPs) are promising drug targets for treating a wide range of diseases such as diabetes, cancer, and neurological disorders, but their conserved active sites have complicated the design of selective therapeutics. This study examines the allosteric inhibition of PTP1B by amorphadiene (AD) and α-bisabolene(AB), terpenoid hydrocarbons that are unusually selective inhibitors. Molecular dynamics (MD) simulations carried out in this study suggest that both AD and AB can stably sample multiple neighboring sites on the allosterically influential C-terminus of the catalytic domain.