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Design, synthesis and characterization of highly potent flavonoid dimers in reversing P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP)-mediated cancer drug resistance


Novel Flavonoid Dimers for Reversing Cancer Drug Resistance

Multidrug resistance (MDR) in cancer is a major problem in chemotherapy. We have designed small molecules to reverse it. Membrane proteins P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) pump drugs out of cancer cells and reduce chemotherapy efficacy. We have designed, synthesized and characterized novel diet-derived flavonoid dimers which can target P-gp and BCRP’s dimeric structure. Due to the unique design of dimeric in structure which can specifically bind to the pseudodimeric P-gp and BCRP, these flavonoid dimers can inhibit P-gp and BCRP, and reverse cancer drug resistance with very high potency (inhibiting BCRP at < 1 nM) and low toxicity (therapeutic index of 1x105 ). 

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