The present invention relates HMG-CoA reductase degradation inducing compounds. Specifically, the present invention relates a bifunctional compound in which a HMG-CoA reductase binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention also relates a...
For example, high sterol concentrations can stimulate degradation of the rate-limiting cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, HMGCR). HMGCR is broken down by the endoplasmic reticulum membrane–associated protein complexes consisting of insulin-...
reductase (HMGR, considered as rate limiting). Cholesterol accelerated the proteasomal degradation of SM which required the N-terminal domain, partially conserved in vertebrates but not in lower organisms. Unlike HMGR, SM degradation is not mediated by Insig, 24,25-dihydrolanosterol, or side-chain...