SKLB054

SKLB054 is a novel, potent small-molecule inhibitor of Janus kinase 2 (JAK2) with an IC50 of 3 nM. Developed by Sichuan University, it is designed to target myeloproliferative neoplasms (MPNs) harboring the JAK2V617F mutation, such as primary myelofibrosis, polycythemia vera, and essential thrombocythemia. In preclinical studies, SKLB054 has demonstrated the ability to inhibit the proliferation of JAK2V617F-dependent cell lines, induce G2/M cell cycle arrest, and promote apoptosis. It also suppresses the phosphorylation of JAK2 and downstream signaling proteins in the JAK-STAT pathway, including STAT3, STAT5, and ERK. In vivo, SKLB054 significantly reduces splenomegaly and prolongs survival in MPN mouse models without showing obvious toxicity, demonstrating superior efficacy compared to ruxolitinib.