biostudies-literatureUnknown9Ferraro GRegione CampaniaArtemetin is a valuable 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled and applied for identifying the artemetin target(s) to inspect its mechanism of action, based on drug affinity-responsive target stability and targeted limited proteolysis. Both approaches point to the disclosure of filamins A and B as direct artemetin targets in HeLa cell lysates, also giving detailed insights into the ligand/protein-binding sites. Interestingly, also 8-prenyl-artemetin, which is an artemetin more permeable semisynthetic analog, directly interacts with filamins A and B. Both cFrontiers in molecular biosciences964295https://www.ebi.ac.uk/biostudies/studies/S-EPMC9452882biostudies-literatureDrug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid.PMC9452882Stork BMorretta EMonti MCMinassi ASalamone SBelvedere RPollastro FTosco AFerraro GPetrella AfalseDrug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid.Artemetin is a valuable 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled and applied for identifying the artemetin target(s) to inspect its mechanism of action, based on drug affinity-responsive target stability and targeted limited proteolysis. Both approaches point to the disclosure of filamins A and B as direct artemetin targets in HeLa cell lysates, also giving detailed insights into the ligand/protein-binding sites. Interestingly, also 8-prenyl-artemetin, which is an artemetin more permeable semisynthetic analog, directly interacts with filamins A and B. Both c2022-01-01T00:00:00Z20222026-04-08T12:00:18.752Z2025-02-19T04:38:33.327ZS-EPMC94528823609005510.3389/fmolb.2022.964295