SK-124

SK-124 is a potent small molecule inhibitor of the Salt-Inducible Kinase (SIK) family, specifically targeting SIK1, SIK2, and SIK3. Developed by researchers at Massachusetts General Hospital and Dana-Farber Cancer Institute, SK-124 acts on the SIK-CRTC-HDAC signaling axis. While initially investigated for its potential to promote bone formation and treat osteoporosis, recent studies have demonstrated its efficacy in controlling Natural Killer (NK) cell malignancies. SK-124 has been shown to significantly reduce the production of inflammatory cytokines (IFNγ, TNFα) and cytotoxic molecules (Granzyme B) in NK cells. In preclinical models of extranodal NK-cell lymphoma (ENKL) and aggressive NK leukemia (ANKL), SK-124 monotherapy suppressed tumor growth and improved survival by downregulating STAT5 activation and inhibiting MYC and E2F target pathways.