SM-06-09

SM-06-09 is a novel, highly selective small molecule inhibitor of histone deacetylase 6 (HDAC6) currently in preclinical development for cancer immunotherapy. Developed through a collaboration involving Georgetown University, the University of Illinois at Chicago, and the Institute of Biotechnology of the Czech Academy of Sciences, SM-06-09 was identified via in silico and macrophage-based screening of HDAC6 inhibitor derivatives. The compound functions by modulating the tumor microenvironment, specifically reprogramming tumor-associated macrophages (TAMs) from a pro-tumoral M2-like phenotype to an anti-tumoral M1-like phenotype. This epigenetic modulation enhances macrophage phagocytosis of tumor cells and improves antigen cross-presentation via MHC class I. In preclinical models of melanoma, SM-06-09 has demonstrated significant anti-tumor activity both as a monotherapy and in combination with anti-PD1 checkpoint inhibitors.