Drug Repurposing: Deferasirox Inhibits the Anti-Apoptotic Activity of Mcl-1. - Archive ouverte HAL Access content directly
Journal Articles Drug Design, Development and Therapy Year : 2021

Drug Repurposing: Deferasirox Inhibits the Anti-Apoptotic Activity of Mcl-1.

Ludovic Carlier
Delphine Ravault


Introduction: With the aim of repositioning commercially available drugs for the inhibition of the anti-apoptotic myeloid cell leukemia protein, Mcl-1, implied in various cancers, five molecules, highlighted from a published theoretical screening, were selected to experimentally validate their affinity toward Mcl-1. Results: A detailed NMR study revealed that only two of the five tested drugs, Torsemide and Deferasirox, interacted with Mcl-1. NMR data analysis allowed the complete characterization of the binding mode of both drugs to Mcl-1, including the estimation of their affinity for Mcl-1. Biological assays evidenced that the biological activity of Torsemide was lower as compared to the Deferasirox, which was able to efficiently and selectively inhibit the antiapoptotic activity of Mcl-1. Finally, docking and molecular dynamics led to a 3D model for the Deferasirox:Mcl-1 complex and revealed the positioning of the drug in the Mcl-1 P2/P3 pockets as well as almost all synthetic Mcl-1 inhibitors. Interestingly, contrary to known synthetic Mcl-1 inhibitors which interact through Arg263, Deferasirox, establishes a salt bridge with Lys234. Conclusion: Deferasirox could be a potential candidate for drug repositioning as Mcl-1 inhibitor.

Dates and versions

hal-03576776 , version 1 (16-02-2022)



Asma Bourafai-Aziez, Mohammed Benabderrahmane, Hippolyte Paysant, Louis-Bastien Weiswald, Laurent Poulain, et al.. Drug Repurposing: Deferasirox Inhibits the Anti-Apoptotic Activity of Mcl-1.. Drug Design, Development and Therapy, 2021, 15, pp.5035-5059. ⟨10.2147/dddt.s323077⟩. ⟨hal-03576776⟩
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