DZNep : A Methyltransferase Modulator for Disease Mitigation

ABSTRACT

While commonly described as an inhibitor of the histone methyltransferase EZH2, the compound 3‐deazaneplanocin A (DZNep) functions as an inhibitor of S‐adenosylhomocysteine hydrolase (SAHH), leading to pan‐methyltransferase inhibition affecting over 150 individual enzyme targets. DZNep has been associated with significant benefits in limiting the development of multiple diseases in animal models. This review synthesizes evidence from preclinical studies demonstrating DZNep's therapeutic potential across multiple disease contexts. The compound shows particular promise as an anticancer and antifibrotic agent. DZNep exhibits consistent anti‐inflammatory effects across diverse disease models. The compound shows a favorable safety profile at therapeutic doses, though comprehensive toxicology data remain limited to short‐term animal studies. While some effects correlate with EZH2 inhibition, the breadth of DZNep's therapeutic activity suggests mechanisms extending beyond this single target. Clinical translation remains the critical next step for validating DZNep's potential and safety as a multi‐target therapeutic agent capable of mitigating diverse pathological processes through methyltransferase modulation.