A computational study of the inhibition mechanisms of P-glycoprotein mediated paclitaxel efflux by kinase inhibitors.

ABSTRACT:

Background

Drug resistance mediated by P-glycoprotein (P-gp) renders many cancer therapies ineffective. One P-gp substrate is the widely used chemotherapy drug paclitaxel. Co-administration of paclitaxel and another drug that inhibits P-gp may enhance the therapeutic effectiveness of paclitaxel by preventing its efflux from tumor cells.

Results

Here we present a computational approach that combines docking studies with mass action kinetic modeling to investigate how kinase inhibitors may inhibit P-gp mediated paclitaxel efflux. The results show that the inhibition can be attributed to competition between paclitaxel and a tyrosine kinase inhibitor (TKI) for the substrate binding domain (SBD) as well as competition between the kinase inhibitor and ATP for the nuclear (ATP) bin

SUBMITTER: Bender J 

PROVIDER: S-EPMC5699195 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature