Cmpd 81

Cmpd 81 is a **small molecule sterol analog** identified as a potent inducer of **3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, HMGCR) degradation**. It works by stimulating the ubiquitination and subsequent degradation of HMG-CoA reductase in an Insig-dependent manner, reducing statin-induced accumulation of this enzyme, thus providing a novel mechanism to reduce cholesterol biosynthesis. Cmpd 81 was shown to lower cholesterol and reduce atherosclerotic plaques in murine models, acting alone or synergistically with statins. The drug represents a new approach for treating cardiovascular disease via pharmacological **targeted protein degradation** of HMG-CoA reductase, rather than direct inhibition alone[1].