LKY250

LKY250 is a first-in-class small-molecule inhibitor targeting the interaction between death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2, also known as STK17B) and serine/arginine-rich splicing factor 6 (SRSF6), as well as DRAK2 phase separation. Developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, LKY250 is designed to treat metabolic dysfunction-associated steatohepatitis (MASH). Under lipotoxic stress, DRAK2 undergoes aberrant liquid-to-solid phase transition, forming condensates that sequester SRSF6 and spliceosomal components, leading to widespread splicing errors and mitochondrial dysfunction. By disrupting the DRAK2-SRSF6 interaction and DRAK2 condensation, LKY250 restores splicing fidelity, preserves mitochondrial integrity, and attenuates hepatic inflammation and fibrosis.