3-deazaneplanocin A

3-deazaneplanocin A (DZNep) is a carbocyclic adenosine analog that acts as a potent inhibitor of S-adenosyl-L-homocysteine (SAH) hydrolase. By blocking this enzyme, DZNep causes an accumulation of SAH, which subsequently inhibits S-adenosylmethionine (SAM)-dependent methyltransferases through product inhibition. Its most significant epigenetic effect is the indirect inhibition of the Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2). This leads to a global reduction in histone H3 lysine 27 trimethylation (H3K27me3) and the depletion of PRC2 proteins. DZNep has been extensively studied in preclinical models for its ability to induce apoptosis in cancer cells, reverse epithelial-mesenchymal transition (EMT), and reprogram microRNA expression, particularly in pancreatic ductal adenocarcinoma and various hematological malignancies.

Other names

3-deazaneplanocin A3-Deazaneplanocin-A