Pharmacology
Multi-stage virtual screening identifies five novel CETP inhibitor lead compounds, confirmed active by biochemical assay (BMC Chem 2024)
Original title: Discovery of novel cholesteryl ester transfer protein (CETP) inhibitors by a multi-stage virtual screening
A drug discovery study used multi-stage virtual screening to identify novel CETP inhibitors. Molecular docking and molecular dynamics simulations revealed binding patterns and narrowed an initial pool to the top 50 compounds by predicted binding affinity, then to 26 compounds after protein-ligand interaction analysis. A CETP inhibition assay confirmed inhibitory activity for the selected compounds, and molecular dynamics simulations showed structurally stable protein-ligand complexes with an unchanged binding site. Five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193 and AN-465/14952302) emerged as promising leads for further CETP inhibitor drug development. Early-stage computational and in vitro discovery work, with no animal or clinical data.
Original abstract
Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity. Protein-ligand interaction analyses were performed, leading to the selection of 26 compounds for further evaluation. A CETP inhibition assay confirmed the inhibitory activities of the selected compounds. The results of the MD simulations revealed the structural stability of the protein-ligand complexes, with the binding site remaining significantly unchanged, indicating that the five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193, and AN-465/14952302) identified have the potential as active CETP inhibitors and are promising leads for drug development.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.