SM13797

SM13797 is a novel, ultra-selective small molecule inhibitor of Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and 1B (DYRK1B), developed by Biosplice Therapeutics. It is primarily being investigated for the treatment of acute myeloid leukemia (AML). The drug's mechanism involves disrupting DYRK1A-mediated phosphorylation of endocytic regulators, specifically the E3 ubiquitin ligase CBL. This disruption promotes the endocytosis and subsequent lysosomal degradation of CD47, a macrophage checkpoint protein often upregulated by AML cells to evade immune surveillance. By reducing cell surface CD47 abundance, SM13797 restores the ability of macrophages to recognize and phagocytose leukemia cells. Preclinical evidence indicates that SM13797 treatment reduces tumor burden and extends survival in AML xenograft models, highlighting its potential as an innate immunotherapy.