3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1)

3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a cytosolic enzyme that catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA to generate HMG-CoA, a key intermediate in the mevalonate pathway, which is essential for cholesterol biosynthesis and production of other isoprenoids[1][4][5]. HMGCS1 activity is tightly regulated both transcriptionally and posttranslationally and has roles in cellular lipid homeostasis[1][3]. Recent evidence implicates HMGCS1 as a significant factor in cancer, particularly in promoting cell proliferation, maintaining cancer stem cell populations, and conferring chemoresistance[1][2]. Its upregulation is associated with aggressive tumor phenotypes and therapeutic resistance; thus, HMGCS1 is emerging as a novel therapeutic target in oncology, with experimental inhibitors in development[1][2][3]. Additionally, dysregulation of HMGCS1 is linked to metabolic and cardiovascular diseases through its central role in lipid metabolism[3][4][5].

Other names

Hydroxymethylglutaryl-CoA synthase, cytoplasmicHMGCS1HMGCSHMG-CoA synthase3-hydroxy-3-methylglutaryl coenzyme A synthase3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble)

Enzyme inhibition to reduce mevalonate pathway activity and cholesterol synthesis. Possible novel mechanism in cancer therapy by inhibiting metabolic adaptation and cancer stem cell properties.