Antipsychotic fluphenazine found to hit LYN kinase and trigger ferroptosis in lung adenocarcinoma
- A Connectivity Map screen flagged the antipsychotic fluphenazine as a candidate against lung adenocarcinoma, motivated by the safety record and brain penetration of CNS drugs.
- Fluphenazine binds LYN kinase directly, with a specific leucine residue as the key contact, and curbs both tumour cell growth and spread; LYN is notably abundant in lung cancer.
- Blocking LYN dampens FAK signalling and lowers GPX4, pushing cells into ferroptosis, which supports repurposing brain-penetrant drugs in oncology.
💡 Points Based on the abstract
Phenothiazines are notoriously promiscuous, so a docking-plus-binding story on LYN doesn't yet tell me LYN is the driver rather than one of many hits. Worse, antitumour effects typically need low-micromolar exposure, which sits above what fluphenazine reaches at tolerated antipsychotic doses. I'd want in vivo exposure and a kinase selectivity panel before spending more.