ArticleThe Journal of biological chemistry2012
Crystal structures of cholesteryl ester transfer protein in complex with inhibitors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Lipid-Lowering Efficacy and Adverse Events of CETP Inhibitor Combination Therapy: A Systematic Review and Network Meta-Analysis.Journal of cardiovascular pharmacology · 2026Pooled it
- In silico discovery of CETP inhibitors from ZINC15 compounds using docking, ADMET filtering, and molecular dynamics simulations.Research in pharmaceutical sciences · 2026Article
- Efficacy and safety of obicetrapib in patients at high cardiovascular risk: a systematic review, meta-analysis, and meta-regression.Annals of medicine and surgery (2012) · 2026Article
- Phospholipids that Plug the Pores of Cholesteryl Ester Transfer Protein Control Its Triglyceride Transfer.Computational and structural biotechnology journal · 2026Article
- Integrated Approach towards Potential Therapeutic Agent for Inflammation-Mediated CVD Utilizing Computational and Experimental Studies.Cell biochemistry and biophysics · 2025Article
- Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non-human primate studies and clinical trials.Pharmacology research & perspectives · 2024Review
- Novel Therapeutic Approaches for the Management of Elevated Lipoprotein(a): From Traditional Agents to Future Treatment Options.Life (Basel, Switzerland) · 2024Review
- Obicetrapib: Reversing the Tide of CETP Inhibitor Disappointments.Current atherosclerosis reports · 2024Review
- Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.Current computer-aided drug design · 2024Article
- Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study.International journal of molecular sciences · 2023Article
- Structure-based mechanism and inhibition of cholesteryl ester transfer protein.Current atherosclerosis reports · 2023Review
- Cholesteryl ester transfer protein inhibitors: from high-density lipoprotein cholesterol to low-density lipoprotein cholesterol lowering agents?Cardiovascular research · 2022Article
- Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels.International journal of molecular sciences · 2022Review
- Quantitative Models of Lipid Transfer and Membrane Contact Formation.Contact (Thousand Oaks (Ventura County, Calif.)) · 2022Article
- Dimethylaminophenyl Hydrazides as Inhibitors of the Lipid Transport Protein LprG in Mycobacteria.ACS infectious diseases · 2020Article
- Remote homology searches identify bacterial homologues of eukaryotic lipid transfer proteins, including Chorein-N domains in TamB and AsmA and Mdm31p.BMC molecular and cell biology · 2019Article
- Cholesteryl ester transfer protein and its inhibitors.Journal of lipid research · 2018Review
- Assessing the mechanisms of cholesteryl ester transfer protein inhibitors.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Article
- How cholesteryl ester transfer protein can also be a potential triglyceride transporter.Scientific reports · 2017Article
- Comparative studies of three cholesteryl ester transfer proteins and their interactions with known inhibitors.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human plasma cholesteryl ester transfer protein (CETP) transports cholesteryl ester from the antiatherogenic high-density lipoproteins (HDL) to the proatherogenic low-density and very low-density lipoproteins (LDL and VLDL). Inhibition of CETP has been shown to raise human plasma HDL cholesterol (HDL-C) levels and is potentially a novel approach for the prevention of cardiovascular diseases. Here, we report the crystal structures of CETP in complex with torcetrapib, a CETP inhibitor that has been tested in phase 3 clinical trials, and compound 2, an analog from a structurally distinct inhibitor series. In both crystal structures, the inhibitors are buried deeply within the protein, shifting the bound cholesteryl ester in the N-terminal pocket of the long hydrophobic tunnel and displacing the phospholipid from that pocket. The lipids in the C-terminal pocket of the hydrophobic tunnel remain unchanged. The inhibitors are positioned near the narrowing neck of the hydrophobic tunnel of CETP and thus block the connection between the N- and C-terminal pockets. These structures illuminate the unusual inhibition mechanism of these compounds and support the tunnel mechanism for neutral lipid transfer by CETP. These highly lipophilic inhibitors bind mainly through extensive hydrophobic interactions with the protein and the shifted cholesteryl ester molecule. However, polar residues, such as Ser-230 and His-232, are also found in the inhibitor binding site. An enhanced understanding of the inhibitor binding site may provide opportunities to design novel CETP inhibitors possessing more drug-like physical properties, distinct modes of action, or alternative pharmacological profiles.
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Registered trials
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.