Abstract

Design of inhibitors of P-glycoprotein still represents a challenging task for medicinal chemists. The polyspecificity of the transporter combined with the limited structural information renders rational drug design approaches rather ineffective. Within this article we will exemplify how recent insights into structure and mechanism of Pglycoprotein may aid in design of potent inhibitors. P >

Keywords: Cyclic peptide P-glycoprotein inhibitor, ATP-binding cassette, Nucleotide binding domain, Transmembrane domain, Central nervous system, Blood brain barrier, Breast cancer related protein, Positron emission tomography, Single-photon emission computed tomography, Cytochrome P450-3A4, Multidrug resistance, MDR, Protein-ligand interaction fingerprints, Serotonine reuptake transporter, Dopamine transporter, Norepinephrine transporter, Structure activity relationship, Radiolabeled P-gp substrates, SAV1866, Ligand docking, Quinazolinones, GABAA receptor, Pharmacophore modeling, NCI-60 screening, ATPbinding site, Tyrosine kinases (TKs), Nilotinib, Dasatinib, Bosutinib, ATPases