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A calcineurin antifungal strategy with analogs of FK506
Mitchell Nambu1, Jonathan A Covel1, Mili Kapoor1
1Amplyx Pharmaceuticals, 3210 Merryfield Row, San Diego, CA 92121, United States.
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.
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