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Antimalarial drugs such as pamaquin are oxidizing compounds that deplete reduced glutathione

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Owing to the abovementioned reasons, it is difficult to find highly selective DUB inhibitors, which explains why most DUB inhibitors are multitargeted and are likely to cause intolerable side effects 162

Additionally, PARP inhibitors (PARPi) demonstrate significant clinical efficacy in BRCA-mutated patients (124), but emerging resistance limits their long-term effectiveness (125), Patients may develop resistance through multiple mechanisms, such as secondary BRCA gene mutations or restoration of DNA repair pathways (126)

doi: 10.1016/j.jacc.2018.04.051