| Hazard Information | Back Directory | [Uses]
TP0480066 is a selective topoisomerase II inhibitor with IC50s of 1.10 and 62.89 nM for DNA gyrase and topo IV, respectively. TP0480066 shows good activity of againsting various bacterial species including drug-resistant strains. TP0480066 also exhibits potent inhibitory activity to N. gonorrhoeae, can be used in study of gonorrhea[1][2]. | [in vivo]
TP0480066 (100 mg/kg; s.c; once) demonstrates Cmax, Tmax, t1/2, and AUC0-24 h values of 12400 ng/mL, 0.250 h, 6.79 h, 16000 h?ng/mL, respectively[2].
TP0480066 (1, 3, 10, 30, 100 mg/kg; s.c.; single) inhibits (30, 100 mg/kg) both N. gonorrhoeae ATCC 49226 and NCTC 13479 at 24 h and in a dose-dependent manner in mice[2]. | Animal Model: | Female Slc:ICR mice[1] | | Dosage: | 100 mg/kg | | Administration: | Subcutaneous injection, once. | | Result: | 1.19Pharmacokinetic Parameters of TP0480066 in Female Slc:ICR mice (n=3)[1].
| Tmax (h) | Cmax (ng/mL) | AUC0-24 (ng/mL?h) | t1/2 (h) | | SC (100 mg/kg) | 0.250 | 12400 | 16000 | 6.79 |
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| Animal Model: | Female BALB/c mice (6-week-old; genital tract infection model)[2] | | Dosage: | 1, 3, 10, 30 and 100 mg/kg | | Administration: | Subcutaneous administration; single. | | Result: | Significantly decreased mean viable cell counts of N. gonorrhoeae ATCC 49226 and NCTC 13479 when at 30, 100 mg/kg. |
| [IC 50]
Topoisomerase II; DNA gyrase: 1.10 nM (IC50); topo IV: 62.89 nM (IC50) | [References]
[1] Ushiyama F, et al. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors. Bioorg Med Chem. 2020 Nov 15;28(22):115776. DOI:10.1016/j.bmc.2020.115776
[2] Masuko A, et al. In Vitro and In Vivo Activities of TP0480066, a Novel Topoisomerase Inhibitor, against Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02145-20. DOI:10.1128/AAC.02145-20 |
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