title: Structure-activity relationships and in silico models of P-glycoprotein (ABCB1) inhibitors.
abstract: 1. The efflux pump p-glycoprotein (P-gp/ABCB1) has received enormous attention in drug (xenobiotic) disposition due to its role in modulation of the drug availability and in protection of sensitive organs. 2. P-gp mediated efflux is one of main mechanisms for multidrug resistance in cancer cells. A main approach to reverse the resistance and restore the drug efficacy is to use specific inhibitors of P-gp that suppress the efflux activity. 3. This review summarizes the binding capabilities of known chemical inhibitors based on the analyses of structure-activity relationships, and computational modeling of the inhibitors as well as the binding site of P-gp protein. 4. The molecular models will facilitate the design of lead inhibitors as drug candidates. Also, it helps scientists in early drug discovery phase to synthesize chemical series with better understanding of their P-gp binding liabilities.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University , Guangzhou, Guangdong , China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Liu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Ma
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D001577:Benzophenones / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D011405:Propafenone / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001577:Benzophenones; D011405:Propafenone; C047723:benzophenone