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Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein (2012–2015)

Abstract:
Cancers expressing the multidrug transporter P-glycoprotein (P-gp) exhibit chemotherapy resistance. The clinical impact of P-gp is so profound that the National Cancer Institute (USA) 'profiles' all anticancer drugs for transport by P-gp, primarily because the precise mechanism by which P-gp binds and transports drugs is currently unknown. The proposal aims to understand, in molecular detail, how different drugs and inhibitors enter and bind to P-gp. To achieve this, a combination of computational modelling techniques and binding assays will be used. The research will provide the information needed to predict how different drugs interact pharmacokinetically with P-gp, a major step in our understanding of P-gp mediated multidrug resistance.
Grant type:
ARC Discovery Early Career Researcher Award
Researchers:

  • Professor Megan O'Mara

    Professorial Research Fellow and Gr
    Australian Institute for Bioengineering and Nanotechnology
    Affiliate Professor of School of Ch
    School of Chemistry and Molecular Biosciences
    Faculty of Science
    Affiliate of ARC COE for Innovation
    ARC Centre of Excellence for Innovations in Peptide and Protein Science
    Institute for Molecular Bioscience
Funded by:
Australian Research Council