| Literature DB >> 28412204 |
Mitchell Nambu1, Jonathan A Covel2, Mili Kapoor2, Xiaoming Li2, Molly K Moloney2, Mehdi M Numa2, Quinlyn A Soltow2, Michael Trzoss2, Peter Webb2, Robert R Webb2, Mitchell Mutz3.
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.Entities:
Keywords: Antifungal; Aspergillosis; Calcineurin; FK506; FKBP12; Immunosuppressant; Tacrolimus
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Year: 2017 PMID： 28412204 DOI： 10.1016/j.bmcl.2017.04.004
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823