Carbene reactive metabolite explains the hepatotoxicity of the hot flashes drug fezolinetant: A DFT investigation.

Fezolinetant, the first-in-class hot flashes drug, was flagged in September 2024 by US-FDA for liver injury. It is alarming that an FDA-approved drug shows liver toxicity within a year. Fezolinetant's metabolic pathways and metabolites are not disclosed in the FDA label, clinical trial, or other literature reports.

An overview of compound properties, multiparameter optimization, and computational drug design methods for PARP-1 inhibitor drugs.

Breast cancer treatment with PARP-1 inhibitors remains challenging due to emerging toxicities, drug resistance, and unaffordable costs of treatment options. How do we invent strategies to design better anti-cancer drugs? A part of the answer is in optimized compound properties, desirability functions, and modern computational drug design methods that drive selectivity and toxicity and have not been reviewed for PARP-1 inhibitors. Nonetheless, comparisons of these compound properties for PARP-1 inhibitors are not available in the literature.