Treatment of histoplasmosis with MK-991 (L-743,872).
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.
Graybill
J R
JR
The University of Texas Health Science Center at San Antonio, 78284, USA. GRAYBILL@UTHSCSA.EDU
Najvar
L K
LK
Montalbo
E M
EM
Barchiesi
F J
FJ
Luther
M F
MF
Rinaldi
M G
MG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000077336:Caspofungin; D004195:Disease Models, Animal; D054714:Echinocandins; D006658:Histoplasma / Q000187:drug effects; D006660:Histoplasmosis / Q000188:drug therapy*; D007121:Immunocompetence; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D000077336:Caspofungin