BTZ043 - Bacterial 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBTZ043Cat. No.: HY-13579CAS No.: 1161233-85-7分式: CHFNOS分量: 431.39作靶點(diǎn): Bacterial作通路: Anti-infection儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 13.3 mg/mL (30.83 mM; Need ultrasonic and w

2、arming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.80 mM); Suspended solution; Need ultrasonic2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.80 mM); Suspended solution; Need ultrasonic3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您邊的抑

3、制劑師www.MedChemESolubility: 2.5 mg/mL (5.80 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BTZ043是DprE1 的抑制劑，它對(duì)結(jié)核分枝桿菌H37Rv (M. tuberculosis H37Rv) 和恥垢分枝桿菌(Mycobacterium smegmatis) 的 MIC 值分別為 2.3 nM 和 9.2 nM。IC50 & Target DprE1 1.體外研究 The MIC of BTZ043 against M. tuberculosis H37Rv and Mycobacterium smegma

4、tis are 1 ng/mL (2.3 nM) and4 ng/mL (9.2 nM), respectively 2. The in vitro activity of BTZ043 against 30 Nocardia brasiliensis isolates isalso tested. The MIC50 and MIC90 values for BTZ043 are 0.125 and 0.25 g/mL. The MIC for N. carneaATCC 6847 is 0.003g/mL, for N. transvalensis ATCC 6865 is 0.003g/

5、mL, for N. brasiliensis NCTC10300 is0.03 g/mL, and for N. brasiliensis HUJEG-1 is 0.125g/mL. The MIC value for M. tuberculosis H37Rv is0.000976 g/mL. The MIC value of BTZ-043 is 64 g/mL for Escherichia coli ATCC 25922 and S. aureusATCC 29213 3.體內(nèi)研究 Four weeks of treatment with BTZ043 reduces the bac

6、terial burden in the lungs and spleens by 1 and 2 logs,respectively, at the concentrations used. Additional results suggest that BTZ043 efficacy is time-rather thandose-dependent. Acute (5 g/kg) and chronic (25 and 250 mg/kg) toxicology studies in uninfected mice showthat, even at the highest dose t

7、ested, there are no adverse anatomical, behavioral, or physiological effectsafter one month 2.PROTOCOLAnimal Mice 2Administration 2 Animal efficacy is determined in a standard mouse infection model. BALB/c mice are infected with a lowbacillary load (200 CFU) of M. tuberculosis H37Rv via aerosol. Tre

8、atment started four-weeks post infection.Mice are dosed by gavage with 37.5, or 300 mg of BTZ043, per kg body weight, in carboxymethyl celluloseformulation (0.25%), once daily, six times/week, for four weeks. Control and treated mice are sacrificed,lungs and spleens homogenized and dilutions plated

9、for enumeration of viable bacilli 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Vadim Makarov et al. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 fromMycobacterium tuberculosis. AntimicrobAgents Chemother, 2015 Aug

10、, 59(8): 4446-4452.2. Makarov V, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science. 2009 May8;324(5928):801-4.3. Norma Alejandra Gonzlez-Martnez et al. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis.PLoS Negl Trop Dis, 2015 Oct, 9(10): e0004022.McePdfHeight2/2 Master of Small Molecules 您邊的抑制劑師www.MedChemECaution: Product has not been fully