hymeglusin

Hymeglusin is a fungal polyketide β-lactone metabolite isolated from various species including *Fusarium*, *Nigrospora*, and *Clonostachys*. It is a potent and specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase (HMGCS), a key enzyme in the mevalonate pathway. Hymeglusin acts by forming a covalent thioester adduct with the active site cysteine residue of the enzyme, effectively blocking the production of HMG-CoA. It inhibits both eukaryotic isoforms (cytosolic HMGCS1 and mitochondrial HMGCS2) as well as the prokaryotic version (mvaS). Research has demonstrated its potential in treating acute myeloid leukemia (AML) and lung squamous cell carcinoma by inducing ferroptosis and enhancing chemosensitivity. Furthermore, it has been shown to circumvent β-lactam resistance in methicillin-resistant *Staphylococcus aureus* (MRSA). While it is a widely used chemical probe in mechanistic studies, its therapeutic development is currently limited by poor stability in serum.

Other names

hymeglusin