ArticleAntimicrobial agents and chemotherapy2011
Preclinical characterization of naturally occurring polyketide cyclophilin inhibitors from the sanglifehrin family.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Exploring the Synthetic Potential of Horner-Wadsworth-Emmons Reaction Toward the Synthesis of Polyketide Based Natural Products: A Review.Topics in current chemistry (Cham) · 2025Review
- Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV.Nature communications · 2025Article
- Sanglifehrin A mitigates multiorgan fibrosis by targeting the collagen chaperone cyclophilin B.JCI insight · 2024Article
- The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity.Viruses · 2023Article
- Review
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Furanoditerpenes fromACS chemical neuroscience · 2022Article
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- Medicinal chemistry strategies toward host targeting antiviral agents.Medicinal research reviews · 2020Review
- Cyclophilin Inhibitor NV556 Reduces Fibrosis and Hepatocellular Carcinoma Development in Mice With Non-Alcoholic Steatohepatitis.Frontiers in pharmacology · 2019Article
- Evaluation of the Protective Effects of Sarains on HNeurotoxicity research · 2017Article
- Chaperones in hepatitis C virus infection.World journal of hepatology · 2016Review
- The role of immunophilins in viral infection.Biochimica et biophysica acta · 2015Article
- Cyclophilin and NS5A inhibitors, but not other anti-hepatitis C virus (HCV) agents, preclude HCV-mediated formation of double-membrane-vesicle viral factories.Antimicrobial agents and chemotherapy · 2015Article
- Hepatitis C NS5A protein: two drug targets within the same protein with different mechanisms of resistance.Current opinion in virology · 2014Review
- Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect.The Journal of biological chemistry · 2013Article
- Host-targeting agents in the treatment of hepatitis C: a beginning and an end?Antiviral research · 2013Review
- Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2013Review
- Cyclophilin inhibitors as antiviral agents.Bioorganic & medicinal chemistry letters · 2013Article
- Cyclophilins as modulators of viral replication.Viruses · 2013Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclophilin inhibitors currently in clinical trials for hepatitis C virus (HCV) are all analogues of cyclosporine (CsA). Sanglifehrins are a group of naturally occurring cyclophilin binding polyketides that are structurally distinct from the cyclosporines and are produced by a microorganism amenable to biosynthetic engineering for lead optimization and large-scale production by fermentation. Preclinical characterization of the potential utility of this class of compounds for the treatment of HCV revealed that the natural sanglifehrins A to D are all more potent than CsA at disrupting formation of the NS5A-CypA, -CypB, and -CypD complexes and at inhibition of CypA, CypB, and CypD isomerase activity. In particular, sanglifehrin B (SfB) was 30- to 50-fold more potent at inhibiting the isomerase activity of all Cyps tested than CsA and was also shown to be a more potent inhibitor of the 1b subgenomic replicon (50% effective concentrations [EC50s] of 0.070 μM and 0.16 μM in Huh 5-2 and Huh 9-13 cells, respectively). Physicochemical and mouse pharmacokinetic analyses revealed low oral bioavailability (F<4%) and low solubility (<25 μM), although the half-lives (t1/2) of SfA and SfB in mouse blood after intravenous (i.v.) dosing were long (t1/2>5 h). These data demonstrate that naturally occurring sanglifehrins are suitable lead compounds for the development of novel analogues that are less immunosuppressive and that have improved metabolism and pharmacokinetic properties.
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Registered trials
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