ArticleChemical science2019
A computationally designed binding mode flip leads to a novel class of potent tri-vector cyclophilin inhibitors.
Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Therapeutic evaluation of artocarpin-enriched extract from Artocarpus heterophyllus heartwood in multiple sclerosis rat model.Inflammopharmacology · 2026Article
- Development of High-Affinity CHD1 Chromodomain Inhibitors.Journal of medicinal chemistry · 2026Article
- Structural and Kinetic Variability of Pathogen Cyclophilins: Functional Diversification and Therapeutic Potential.ACS infectious diseases · 2026Review
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Optimization of Cyclophilin B-Targeted Tri-vector Inhibitors for Novel MASH Treatments.Journal of medicinal chemistry · 2025Article
- Toward Dual Targeting of Catalytic and Gatekeeper Pockets in Cyclophilins Using a Macrocyclic Scaffold.ACS medicinal chemistry letters · 2024Article
- Neuroprotective Effect of 2-(Benzyloxy)arylureas Is Not Related to CypD Inhibition nor Suppression of mPTP Opening.ACS medicinal chemistry letters · 2024Article
- Alchemical Free Energy Workflows for the Computation of Protein-Ligand Binding Affinities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Comparison of Receptor-Ligand Restraint Schemes for Alchemical Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2023Article
- Discovery and molecular basis of subtype-selective cyclophilin inhibitors.Nature chemical biology · 2022Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Sampling Conformational Changes of Bound Ligands Using Nonequilibrium Candidate Monte Carlo and Molecular Dynamics.Journal of chemical theory and computation · 2020Article
- Dynamic design: manipulation of millisecond timescale motions on the energy landscape of cyclophilin A.Chemical science · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Cyclophilins (Cyps) are a major family of drug targets that are challenging to prosecute with small molecules because the shallow nature and high degree of conservation of the active site across human isoforms offers limited opportunities for potent and selective inhibition. Herein a computational approach based on molecular dynamics simulations and free energy calculations was combined with biophysical assays and X-ray crystallography to explore a flip in the binding mode of a reported urea-based Cyp inhibitor. This approach enabled access to a distal pocket that is poorly conserved among key Cyp isoforms, and led to the discovery of a new family of sub-micromolar cell-active inhibitors that offer unprecedented opportunities for the development of next-generation drug therapies based on Cyp inhibition. The computational approach is applicable to a broad range of organic functional groups and could prove widely enabling in molecular design.
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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.