ArticleNature communications2018
Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
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- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Impaired cortical actin dynamics via lanosterol-dependent HMG-CoA reductase downregulation mediates IFN-α-induced mast cell stabilization.The Journal of biological chemistry · 2026Article
- High levels of serum cholesterol increase the risk of developing vessel co-opting tumors in colorectal cancer liver metastases.The FEBS journal · 2026Article
- Isolation, Purification, Structural Characterization of Acidic Polysaccharides fromFoods (Basel, Switzerland) · 2026Article
- Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS.Nature communications · 2026Article
- Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases.Journal of pharmaceutical analysis · 2026Review
- Effects ofFrontiers in immunology · 2026Article
- RNA-Targeted Therapeutics for Lipid Metabolic Disorders: From Bench to Bedside.Research (Washington, D.C.) · 2026Article
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- Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation.bioRxiv : the preprint server for biology · 2025Article
- Integrated Multi-Omics Investigation of Gypenosides' Mechanisms in Lowering Hepatic Cholesterol.Biomolecules · 2025Article
- Pediatric Familial Hypercholesterolemia: Targeting Intestinal Absorption and Other Therapeutic Strategies.Nutrients · 2025Review
- Cholesterol sulfate as a negative regulator of cellular cholesterol homeostasis.Molecules and cells · 2025Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase of reductase protein following statin treatment may attenuate the effect and increase the side effects. Here we present a previously unexplored strategy to alleviate statin-induced reductase accumulation by inducing its degradation. Inspired by the observations that cholesterol intermediates trigger reductase degradation, we identify a potent degrader, namely Cmpd 81, through structure-activity relationship analysis of sterol analogs. Cmpd 81 stimulates ubiquitination and degradation of reductase in an Insig-dependent manner, thus dramatically reducing protein accumulation induced by various statins. Cmpd 81 can act alone or synergistically with statin to lower cholesterol and reduce atherosclerotic plaques in mice. Collectively, our work suggests that inducing reductase degradation by Cmpd 81 or similar chemicals alone or in combination with statin therapy can be a promising strategy for treating cardiovascular disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.