MPK544

MPK544 is a novel small molecule dual inhibitor of histone deacetylase 2 (HDAC2) and histone deacetylase 6 (HDAC6) currently under preclinical investigation for the treatment of pancreatic ductal adenocarcinoma (PDAC). The compound acts by reversing the epithelial-mesenchymal transition (EMT) through the upregulation of E-cadherin, a process mediated by HDAC2 blockade, which significantly reduces the invasive and metastatic capacity of PDAC cells. Additionally, MPK544 inhibits HDAC6, leading to cell cycle arrest and the induction of apoptosis. Research in PANC-1 cell lines and 3D co-culture spheroids has shown that MPK544 can effectively counteract TGF-β-induced downregulation of E-cadherin and inhibit tumor cell invasion by approximately 60%.