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USP24-i-101 + astemizole is an experimental drug combination investigated for overcoming drug resistance in cancer, especially lung cancer. **USP24-i-101** is a small molecule inhibitor of the deubiquitinase USP24, which modulates autophagy, genomic instability, and immune evasion in drug-resistant cancer cells by increasing PD-L1 protein degradation and stabilizing the genome in an autophagy-dependent manner. **Astemizole** is a second-generation, long-acting, non-sedating antihistamine that functions primarily as a histamine H1 receptor antagonist, previously used for allergy symptoms but withdrawn due to cardiac toxicity (QT prolongation via hERG blockade). Recent studies have shown that, in combination, USP24-i-101 and astemizole synergistically re-sensitize drug-resistant lung cancer cells to therapies such as Taxol and Gefitinib, enhancing cytotoxicity and inhibiting drug resistance[1][3][9].
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