GCJ-490A

GCJ-490A (also known as 490A) is a novel, small-molecule pan-histone deacetylase (HDAC) inhibitor developed by the Shanghai Institute of Materia Medica, the Yantai Institute of Materia Medica, and the Shandong Laboratory of Yantai Drug Discovery. It exhibits potent inhibitory activity against HDAC1, HDAC3, and HDAC6. In preclinical studies, GCJ-490A has demonstrated significant anti-tumor efficacy against solid tumors, including non-small cell lung cancer (NSCLC) and breast cancer, both as a monotherapy and in combination with other agents such as EGFR inhibitors (e.g., gefitinib) or anti-PD-1 antibodies. Mechanistically, GCJ-490A promotes histone acetylation at the IKKα promoter, leading to the downregulation of c-Met expression, and reprograms the tumor immune microenvironment by enhancing T-cell cytotoxicity and modulating tumor-associated macrophages toward a pro-inflammatory M1 phenotype.