In vivo activity of the lead compound. (a) Protection in the murine model of hematogenously disseminated candidiasis. Compound 61894700 was administered to a group of mice (n=8) once daily by intraperitoneal injection at 20 mg/kg, starting 2 days before infection with C. albicans via the lateral tail vein. A control group of mice (n=8) received vehicle-only injections. Treatment continued for 7 days post infection. All treated mice survived the infection (P=0.0021 versus untreated), as determined by Kaplan–Meier log-rank tests. (b) Kidney sections from untreated mice showed characteristic kidney lesions of mostly filamentous nature, whereas isolated or small groups of mostly yeast cells were predominant in kidneys from treated mice. (c) Efficacy of compound 61894700 against oral candidiasis. Mice were inoculated orally with C. albicans. One group of mice (n=5) received vehicle only, whereas two additional groups (n=5 each) received treatment with compound 61894700 (20 mg/kg), starting 2 days before infection, either topically (twice daily) or systemically (once daily). The graph depicts the clinical score (from 0 to 4 on the basis of the extent and severity of the tongue lesions) for mice killed 3 days after infection. Statistically significant differences versus control were detected for animals treated topically (P=0.0406) or systemically (P=0.0108), using the one-tailed Mann–Whitney test. (d) Histology shows a filamentous biofilm covering the tongue surface and penetrating deep into the tissues of untreated animals, compared with fewer superficially located yeast cells in tongues from mice treated topically (similar observations were made in animals treated intraperitoneally). Bars=20 μm.