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A calcineurin antifungal strategy with analogs of FK506.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Jun 01; Vol. 27 (11), pp. 2465-2471. Date of Electronic Publication: 2017 Apr 03. - Publication Year :
- 2017
-
Abstract
- A novel antifungal strategy targeting the inhibition of calcineurin is described. To develop a calcineurin based inhibitor of pathogenic fungi, analogs of FK506 were synthesized that were able to permeate mammalian but not fungal cells. Antagonists in combination with FK506 were not immunosuppressive and retained antifungal activity in A. fumigatus. To reduce the dosage burden of the antagonist, murine oral PK was improved an order of magnitude relative to previous FK506 antagonists.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antifungal Agents chemical synthesis
Antifungal Agents pharmacokinetics
Antifungal Agents toxicity
Aspergillus fumigatus drug effects
Calcineurin Inhibitors chemical synthesis
Calcineurin Inhibitors pharmacokinetics
Calcineurin Inhibitors toxicity
Chlorocebus aethiops
Hep G2 Cells
Humans
Interleukin-2 metabolism
Jurkat Cells
Tacrolimus chemical synthesis
Tacrolimus pharmacokinetics
Tacrolimus toxicity
Tacrolimus Binding Protein 1A chemistry
Vero Cells
Antifungal Agents pharmacology
Calcineurin Inhibitors pharmacology
Tacrolimus analogs & derivatives
Tacrolimus pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 27
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 28412204
- Full Text :
- https://doi.org/10.1016/j.bmcl.2017.04.004