Phenotypic screening identifies kenpaullone as a prolymphangiogenic compound to improve heart repair following myocardial infarction.

Kenpaullone enhances cardiac lymphangiogenesis and improves heart function after myocardial infarction by targeting MAP4K4 in mice.

• Why it matters: Current treatments for myocardial infarction do not promote heart tissue regeneration, leading to heart failure. Developing prolymphangiogenic therapies could address this gap and improve recovery outcomes.
• What they did: A phenotypic screen of focused libraries identified kenpaullone as a potent GSK3 inhibitor that activates the ERK pathway and induces lymphatic growth, with target validation pointing to MAP4K4.
• The result: Kenpaullone treatment in a mouse MI model increased cardiac lymphatic vessel growth and improved cardiac function, suggesting its potential as a therapeutic agent for heart repair.