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 EfficiencyProfiles of Benzophenone-Type Inhibitors of the Multidrug TransporterP-Glycoprotein.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 multidrugresistance (MDR) in tumors as well as to influence ADME properties of drugcandidates. Here we synthesized and tested a series of benzophenone derivativesstructurally analogous to propafenone-type inhibitors of P-gp. Some of thecompounds showed ligand efficiency and lipophilic efficiency (LipE) values in therange 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 promisingdrug candidates. Docking studies of selected analogues into a homology model ofP-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.PMID: 22452412 [PubMed - as supplied by publisher]