chaetocin

Chaetocin is a fungal mycotoxin originally isolated from species of the genus Chaetomium. It is a small molecule epigenetic modulator that acts primarily as an inhibitor of lysine-specific histone methyltransferases, including SU(VAR)3-9 (SUV39H1), G9a, and DIM5, with reported IC50 values in the low micromolar range. Chaetocin also inhibits other histone methyltransferases such as SET7 and EZH2 to a lesser extent. Mechanistically, it reduces H3K9 methylation and can reactivate silenced tumor suppressor genes in cancer cells[1][2][3][8]. In addition to its epigenetic effects, chaetocin induces cellular oxidative stress by inhibiting thioredoxin reductase 1 (TrxR1), leading to increased reactive oxygen species (ROS) and selective cytotoxicity toward cancer cells[1][7]. It has demonstrated antitumor activity in various preclinical models by inducing apoptosis, cell cycle arrest (notably at M phase), suppressing self-renewal pathways in cancer stem cells via KMT1A–GATA3–STAT3 signaling inhibition[6], activating the Hippo pathway[9], and inhibiting transketolase activity[5]. While chaetocin shows promise as an anticancer agent in research settings—including for leukemia, bladder cancer stem cells, esophageal squamous cell carcinoma (ESCC), and non-small cell lung cancer—its use remains experimental with no current approval for clinical or therapeutic applications.

Other names

chaetocin