Key result
Dexamethasone demonstrates superior in silico binding affinity to SLC7A11 over control.
Why the study?
Drug-induced cardiotoxicity remains a major challenge in pharmaceutical development, necessitating the identification of protective agents that activate SLC7A11/xCT to defend against oxidative stress and cardiac damage.
Do repurposed approved drugs (such as dexamethasone and prulifloxacin) exhibit superior binding affinity and stability targeting SLC7A11/xCT compared to control compound MC-100093 in silico?
Do repurposed approved drugs (such as dexamethasone and prulifloxacin) exhibit superior binding affinity and stability targeting SLC7A11/xCT compared to control compound MC-100093 in silico?
In silico screening identifies dexamethasone and prulifloxacin as stable, high-affinity candidates targeting the SLC7A11/xCT antiporter, offering potential avenues for experimental validation against drug-induced cardiotoxicity.
Answers are grounded in this paper and cite their sources.
Identified antibiotic candidates for xCT activation merit preclinical testing; leaves open efficacy against drug-induced cardiotoxicity.
Drug-induced cardiotoxicity remains a major challenge in pharmaceutical development, necessitating the identification of protective agents against cardiac damage. The cystine/glutamate antiporter solute carrier family 7 member 11/ cystine-glutamate antiporter (SLC7A11/xCT) plays a crucial role in cellular defense against oxidative stress by facilitating glutathione synthesis. This study utilized in silico drug repurposing to identify potential xCT activators from a library of approved antibiotics. Molecular docking was employed to assess the binding affinity of 355 drugs, with the control compound MC-100093 demonstrating a binding affinity of −6.7 kcal/mol. Thirty-one drugs exhibited stronger binding, with Daunorubicin showing the highest affinity (−10.8 kcal/mol); however, its known cardiotoxicity excluded it from further analysis. Following absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening, seven drugs were selected based on their adherence to Lipinski’s Rule of Five and favorable pharmacokinetic properties. Notably, dexamethasone and prulifloxacin stood out for their favorable binding affinity and stability in molecular dynamics simulations. Compared to the control, dexamethasone exhibited superior binding affinity (−9.2 kcal/mol) and the most favorable total binding free energy (−14.89 kcal/mol), indicating enhanced stability within the xCT complex. This was further supported by its stable interaction profile, reduced structural fluctuations, and favorable drug-likeness properties. These results suggest that dexamethasone promising candidates for repurposing as cardioprotective agents, offering potential therapeutic options for mitigating drug-induced cardiotoxicity. Further experimental validation is needed to confirm their efficacy in-vivo . GRAPHICAL ABSTRACT Selecting compounds with the possibility of cardioprotective activity.
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Alshehri et al. (2026) studied Drug-induced cardiotoxicity (n=355). In silico drug repurposing (dexamethasone and prulifloxacin) vs. Control compound MC-100093 was evaluated on Binding affinity and total binding free energy to SLC7A11/xCT. Dexamethasone showed superior binding affinity (-9.2 vs -6.7 kcal/mol for control) and favorable total binding free energy (-14.89 kcal/mol) to SLC7A11/xCT in silico.
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