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) [1].

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Fungal

T-2307 exhibits potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains[1]. T-2307 shows efficacy in a murine model of candida glabrata infection despite in vitro trailing growth phenomena[2]. Cell Viability Assay[2] Cell 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 mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the ED50 of T-2307 were 0.00755, 0.117, and 0.391 mg/kg, respectively[1]. Animal Model: 4-week-old specific-pathogen-free ICR strain male mice bearing systemic infections with Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus[1]. 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 ED50s 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 ED50s 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 ED50s of T-2307 were 0.391 mg/kg.

[1]. Junichi Mitsuyama, et al.  In vitro and in vivo antifungal activities of T-2307, a novel arylamidine. Antimicrob Agents Chemother. 2008 Apr;52(4):1318-24.

[2]. Eio Yamada, et al.  T-2307 shows efficacy in a murine model of Candida glabrata infection despite in vitro trailing growth phenomena. Antimicrob Agents Chemother. 2010 Sep;54(9):3630-4.