Treatment of Histoplasmosis with MK-991 (L-743,872)

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Abstract
BALB/c nu /+ immunocompetent and athymic ( nu/nu ) mice were infected intravenously with yeast cells of Histoplasma capsulatum . Mice were either given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survival or reduction in tissue counts. MK-991 was protective in immunocompetent mice, prolonging survival and reducing counts in spleen and livers at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modestly effective in athymic mice at a higher dose, 5 mg/kg/day. These studies suggest that MK-991 may be appropriate for clinical development in histoplasmosis.