Inhibitors of ABCG2-mediated multidrug resistance: Lead generation through computer-aided drug design - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2023

Inhibitors of ABCG2-mediated multidrug resistance: Lead generation through computer-aided drug design

Résumé

Human breast cancer resistance protein (BCRP), known also as ABCG2, plays a major role in multiple drug resistance (MDR) in tumor cells. Through this ABC transporter, cancer cells acquire the ability of resistance to structurally and functionally unrelated anticancer drugs. Nowadays, the design of ABCG2 inhibitors as potential agents to enhance the chemotherapy efficacy is an interesting strategy. In this context, we have used computer-aided drug design (CADD) based on available data of a large series of potent inhibitors from our groups as an approach in guiding the design of effective ABCG2 inhibitors. We report therein the results on the use of the FLAPpharm method to elucidate the pharmacophoric features of one of the ABCG2 binding sites involved in the regulation of the basal ATPase activity of the transporter. The predictivity of the model was evaluated by testing three predicted compounds which were found to induce high inhibitory activity of BCRP, in the nanomolar range for the best of them.
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Dates et versions

hal-03939266 , version 1 (14-01-2023)

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Laura Goracci, Alessandra Nurisso, Emile Roussel, Basile Pérès, Vincent Chaptal, et al.. Inhibitors of ABCG2-mediated multidrug resistance: Lead generation through computer-aided drug design. European Journal of Medicinal Chemistry, 2023, 248, pp.115070. ⟨10.1016/j.ejmech.2022.115070⟩. ⟨hal-03939266⟩
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