T-2307

T-2307, an arylamidine, has antifungal activities in vitro and in vivo. T-2307 exhibits broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 μg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 μg/ml), and Aspergillus species (MIC range, 0.0156 to 4 μg/mL). In Vitro T-2307 exhibits potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains. T-2307 shows efficacy in a murine model of candida glabrata infection despite in vitro trailing growth phenomena. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: C. glabrata ATCC 90030 Concentration: 0.000125, 0.00025, 0.0005, 0.001, 0.002, 0.0039, 0.0078, 0.0156, 0.0313, 0.0625, 0.125 μg/mL Incubation Time: 24 and 48 hours Result: C. glabrata exhibited significant trailing growth at concentrations between 0.0039 and 0.125 μg/mL at 48 h. The trailing growth of C. glabrata at 24 h of incubation was similar to that at 48 h. In Vivo In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the ED 50 of T-2307 were 0.00755, 0.117, and 0.391 mg/kg, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 4-week-old specific-pathogen-free ICR strain male mice bearing systemic infections with Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus . Dosage: 0.001, 0.1, 1 mg/kg Administration: Subcutaneously administered; once a day for 7 days, beginning at 2 h after the infection. Result: In the systemic infection caused by Candida albicans , all the control mice died by day 6. Mortality was significantly delayed in mice that were administered T-2307 at a dose of 0.01 mg/kg compared with that in the control mice. The calculated ED 50 s of T-2307were 0.00755 mg/kg. In the systemic infection caused by Cryptococcus neoformans , all the control mice died by day 9. Mortality was significantly delayed in mice administered T-2307 at a dose of 0.1 mg/kg compared with that in the control mice. The calculated ED 50 s of T-2307 were 0.117 mg/kg. In the systemic infection caused by Aspergillus fumigatus , all the control mice died by day 6. Mortality was significantly delayed in mice that were administered T-2307 at a dose of 1 mg/kg compared with that in the control mice. The calculated ED 50 s of T-2307 were 0.391 mg/kg. Form:Solid

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