BTZ043 racemate

• 产品号: S1097
• CAS号: 1161233-85-7
• 分子式: C17H16F3N3O5S
• 分子量: 431.3862496
• 保 存: -20°C

产品别名

• 标题: BTZ043 racemate
• IUPAC标准名: 2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
• IUPAC传统名: 2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one
• 别名: BTZ044; BTZ038

产品登记号

• CAS号: 1161233-85-7

产品性质

• 成盐信息: racemate
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Infection

Biological Activity

• Description: BTZ043 racemate is a decaprenylphosphoryl-β-_D-ribose 2’-epimerase inhibitor acting as a new antimycobacterial agent that kill Mycobacterium tuberculosis.
• Targets: Decaprenylphosphoryl-β-_D-ribose 2’-epim
• In Vitro: By targeting decaprenylphosphoryl-β-_D-ribose 2’-epimerase, BTZ043 abolishes the formation of decaprenylphosphoryl arabinose, leading to cell lysis and death of Mycobacterium tuberculosis. BTZ043 displays similar activity against all clinical isolates of M. tuberculosis, including multidrug-resistant and extensively drug-resistant strains. BTZ043 displays significant activity against M. tuberculosis H37Rv and Mycobacterium smegmatis with MIC of 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively, which is more potent than those of the existing tuberculosis (TB) drugs isoniazid (INH) and ethambutol (EMB) with MIC of 0.02-0.2 μg/mL and 1-5 μg/mL, respectively. BTZ043 is less effective in two different model systems (auxotrophy and starvation) involving metabolically inert M. tuberculosis, indicating that BTZ043 blocks a step in active metabolism similar to isoniazid (INH). BTZ043 treatment in M. smegmatis cells decreases the growth rate rapidly followed by a swelling of the poles and lysis of the cells after a few hours, which is similar but delayed in M. tuberculosis. ^[1] BTZ043 (1/4 MIC 0.375 ng/mL) in combination with TMC207 (1/4 MIC 20 ng/mL) has a stronger cidal effect on M. tuberculosis but not BTZ-resistant M. tuberculosis mutant than TMC207 alone at a concentration of 80 ng/mL. ^[2]
• In Vivo: In a mouse model of chronic tuberculosis, administration of BTZ043 at 37.5 mg/kg or 300 mg/kg for 4 weeks reduces the bacterial burden in the lungs and spleens by 1 and 2 logs, respectively. ^[1]
• Features: More active than EMB against M. tuberculosis.

Protocol

• Protocol: Animal Study ^[1]
• Animal Models: BALB/c mice infected with a low bacillary load (~200 CFU) of M. tuberculosis H37Rv via aerosol
• Formulation: Formulated in carboxymethyl cellulose formulation (0.25%)
• Doses: 37.5 mg/kg, or 300 mg/kg
• Administration: Oral gavage once daily

References

• References: [1] Makarov V, et al. Science, 2009, 324(5928), 801-804.
• References: [2] Lechartier B, et al. Antimicrob Agents Chemother, 2012.

参考文献

• Makarov V, et al. Science, 2009, 324(5928), 801-804.
• Lechartier B, et al. Antimicrob Agents Chemother, 2012.