zaragozic acid A

Zaragozic acid A is a potent, naturally occurring fungal metabolite that acts as a competitive inhibitor of squalene synthase (SQS), the enzyme responsible for the first committed step in sterol biosynthesis. Originally discovered by Merck and GSK (as squalestatin 1), it mimics the intermediate presqualene pyrophosphate to block the conversion of farnesyl pyrophosphate into squalene. This inhibition leads to a significant reduction in cholesterol levels and a redirection of mevalonate pathway intermediates toward other isoprenoids like dolichol and geranylgeranoic acid. While initially investigated as a cholesterol-lowering agent, it is primarily used as a pharmacological tool in research. Studies have demonstrated its potential in treating congenital disorders of glycosylation, inhibiting viral replication (including HCV, Dengue, and Yellow Fever), and suppressing cancer cell proliferation, particularly in prostate and hepatic models. However, it also acts as a glucocorticoid receptor agonist, which can negatively impact wound healing.

Other names

zaragozic acidSqualestatin S1