SKL27969

SKL27969 is a central nervous system (CNS)-penetrant, orally bioavailable small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5). It selectively binds to PRMT5 and inhibits its function, leading to antiproliferative and antineoplastic activities. The drug has demonstrated potent cellular symmetric dimethylarginine (SDMA) inhibition with an IC50 of 3.4 nM and shows broad-spectrum anti-proliferative activity in various cancer cell types, including CNS tumors, solid cancers prone to brain metastasis, other solid cancers, and hematologic malignancies. Designed for brain penetration, it has shown excellent brain exposure in preclinical models. SKL27969 is being developed primarily for the treatment of advanced solid tumors such as glioblastoma multiforme and other difficult-to-treat cancers.