pgp - publications

Predict more pgp - ligand interactions now!

1. J Med Chem. 2012 Mar 27. [Epub ahead of print]

Structure-Activity Relationships, Ligand Efficiency, and Lipophilic Efficiency
Profiles of Benzophenone-Type Inhibitors of the Multidrug Transporter

Jabeen I, Pleban K, Rinner U, Chiba P, Ecker GF.

University of Vienna, Department of Medicinal Chemistry, Althanstrasse 14, 1090,
Vienna, Austria.

The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug
resistance (MDR) in tumors as well as to influence ADME properties of drug
candidates. Here we synthesized and tested a series of benzophenone derivatives
structurally analogous to propafenone-type inhibitors of P-gp. Some of the
compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the
range of compounds which entered clinical trials as MDR modulators.
Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors,
all compounds investigated showed LipE values below the threshold for promising
drug candidates. Docking studies of selected analogues into a homology model of
P-glycoprotein suggest that benzophenones show an interaction pattern similar to
that previously identified for propafenone-type inhibitors.

PMID: 22452412 [PubMed - as supplied by publisher]