A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins.

A zebrafish phenotypic drug screen identified seven compounds, including enoxolone, that lower ApoB-containing lipoproteins, highlighting HNF4α as a key regulator.

• Why it matters: Elevated vascular B-lps are a major cause of cardiovascular disease in humans, but the cellular mechanisms controlling their levels are not fully understood. Understanding these pathways could lead to new therapies.
• What they did: Using the LipoGlo reporter system in zebrafish, approximately 3000 compounds were screened, resulting in 49 hits that lowered ApoB-lps, with seven confirmed through detailed phenotyping and further testing.
• The result: Enoxolone and HNF4α inhibitors reduce B-lp levels only in animals with functional HNF4α, demonstrating that whole-animal screens can rapidly identify mechanisms and potential drug targets for cardiovascular disease.