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BTZ043
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
BTZ043图片
CAS NO:1161233-85-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 431.39
Formula C17H16F3N3O5S
CAS No.1161233-85-7 (S-isomer);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 13.3 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES O=C1N=C(N(CC2)CCC32OC[C@H](C)O3)SC4=C([N+]([O-])=O)C=C(C(F)(F)F)C=C14
Synonyms BTZ043; BTZ 043; BTZ-043.
实验参考方法
In Vitro

In vitro activity: BTZ043, also known as 8-Nitro-benzothiazinones (BTZs), is a potent inhibitor of decaprenyl-phosphoribose-epimerase (DprE1) with MIC values of of 2.3 nM and 9.2 nM for M. tuberculosis H37Rv and Mycobacterium smegmatis, respectively. It can display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. The inhibition of BTZ-resistant DprE1 followed the trend observed in the MIC measurements, with the C387G mutant being more resistant to inhibition by PyrBTZ01, PyrBTZ02, and BTZ043 (7- to 9-fold increases in IC50) than the C387S mutant (2.5- to 4-fold increases in IC50). Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. BTZ043 presented favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. BTZ043 did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency.


Kinase Assay: BTZ043, also known as 8-Nitro-benzothiazinones (BTZs), is a potent inhibitor of decaprenyl-phosphoribose-epimerase (DprE1) with MIC values of of 2.3 nM and 9.2 nM for M. tuberculosis H37Rv and Mycobacterium smegmatis, respectively.


Cell Assay: The MIC of BTZ043 against M. tuberculosis H37Rv and Mycobacterium smegmatis are 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively. The in vitro activity of BTZ043 against 30 Nocardia brasiliensis isolates is also tested. The MIC50 and MIC90 values for BTZ043 are 0.125 and 0.25 μg/mL. The MIC for N. carnea ATCC 6847 is 0.003μg/mL, for N. transvalensis ATCC 6865 is 0.003μg/mL, for N. brasiliensis NCTC10300 is 0.03 μg/mL, and for N. brasiliensis HUJEG-1 is 0.125μg/mL. The MIC value for M. tuberculosis H37Rv is 0.000976 μg/mL. The MIC value of BTZ-043 is>64 μg/mL for Escherichia coli ATCC 25922 and S. aureus ATCC 2921.

In Vivo BTZ-043 were administered at 100 mg/kg twice daily by gavage, and sulfamethoxazole/trimethoprim (SXT), at 100 mg/kg sulfamethoxazole, was used as a positive control
Animal model BALB/c mice infected with a low bacillary load (~200 CFU) of M. tuberculosis H37Rv via aerosol.
Formulation & Dosage Formulated in carboxymethyl cellulose formulation (0.25%); 7.5, or 300 mg/kg; p.o. once daily
References PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022; Science. 2009 May 8;324(5928):801-4.