Macozinone

产品说明书

Print
Chemical Structure| 1377239-83-2 同义名 : PBTZ169
CAS号 : 1377239-83-2
货号 : A713021
分子式 : C20H23F3N4O3S
纯度 : 97%
分子量 : 456.48
MDL号 : MFCD28902203
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 5 mg/mL(10.95 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The essential flavo-enzyme DprE1, decaprenylphosphoryl-β-D-ribose 2-epimerase, produces the sole source of the D-arabinose required for biosynthesis of the key cell wall components arabinogalactan and lipoarabinomannan. PBTZ169, belonging to a new series of piperazine-containing benzothiazinones (PBTZ), is a potent DprE1 inhibitor. PBTZ169 was found to be three- to seven-fold more active than BTZ043 against M. tuberculosis, Mycobacterium bovis BCG, Mycobacterium marinum, Mycobacterium smegmatis, Corynebacterium diphtheriae and Corynebacterium glutamicum. PBTZ169 was found to be 10-times less cytotoxic (TD50 of 58 μg/ml) compared to BTZ043 (TD50 of 5 μg/ml). On incubation with human or mouse microsomes, PBTZ169 showed medium clearance values. Inhibition of M. tuberculosis DprE1 by PBTZ169 was monitored by determining the residual enzyme activity following incubation with a range of concentrations of this compound. Full inhibition of DprE1 was obtained following 5 min incubation with 5 μM PBTZ169. Treatment of infected zebrafish embryos with increasing concentrations of PBTZ169 led to a decrease in the bacterial burden after 5 days. Almost no bacteria were present when infected zebrafish embryos were treated with 25 or 50 nM PBTZ169[3].
作用机制 The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.19mL

0.44mL

0.22mL

10.95mL

2.19mL

1.10mL

21.91mL

4.38mL

2.19mL
参考文献

[1]Makarov V, Neres J, et al. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Aug;59(8):4446-52.

[2]Makarov V, Lechartier B, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med. 2014 Mar;6(3):372-83.

[3]Makarov V, Lechartier B, Zhang M, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med. 2014;6(3):372‐383