Definition

An orally bioavailable small molecule inhibitor of the histone deacetylase 1 (HDAC1)-containing co-repressor of repressor element-1 silencing transcription (CoREST) complex, with potential immunomodulating activity. Upon oral administration, CoREST inhibitor TNG260 binds to CoREST complex and inhibits the catalytic activity of HDAC1, which results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This may reverse immune evasion and resistance to immune checkpoint inhibitors caused by serine-threonine kinase 11 (STK11) mutations. Loss-of-function mutations in STK11 is associated with immune checkpoint inhibitor resistance.