Neoantimycin is a macrocyclic antibiotic isolated from Streptomyces bacteria. The mechanism of action of Neoantimycin is undescribed in the literature. A closely related compound described as an oxidized-type neoantimycin, prunustatin A, is demonstrated to downregulate grp78 transcription and suppress the expression of the GRP 78 molecular chaperone. This suppression affects the role of GRP 78 in promoting protein folding at the endoplasmic reticulum (ER), and suppresses the pro-resistance enhancement of ER stress response by chemotherapy-resistant tumors. The close structural kinship between prunustatin A and Neoantimycin suggests a similar mechanism of action for Neoantimycin toxicity.
