CHIR-090 - Bacterial 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECHIR-090Cat. No.: HY-15460CAS No.: 728865-23-4分式: CHNO分量: 437.49作靶点: Bacterial作通路: Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 30 mg/mL (68.57 mM)* means soluble, but satu

2、ration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2858 mL 11.4288 mL 22.8577 mL5 mM 0.4572 mL 2.2858 mL 4.5715 mL10 mM 0.2286 mL 1.1429 mL 2.2858 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 CHIR-090 is prepared in 0.04% DMSO3.BIOLOGICAL ACTIVITY物活性 CHIR-090种有效，缓慢，亲和强的 LpxC 脱

3、酰酶抑制剂。它与 E. coli LpxC 结合的 Ki 值为 4.0 nM。IC50 & Target Ki: 4 nM (Escherichia coli LpxC) 11/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 CHIR-090 is a potent, slow, tight-binding inhibitor of the LpxC deacetylase from the hyperthermophile Aquifexaeolicus, and it has excellent antibiotic activity

4、 against P. aeruginosa and E. coli, as judged by disk diffusionassays. CHIR-090 is also a two-step slow, tight-binding inhibitor of Escherichia coli LpxC with Ki=4 nM.CHIR-090 at low nM levels inhibits LpxC orthologues from diverse Gram-negative pathogens, includingPseudomonas aeruginosa, Neisseria

5、meningitidis, and Helicobacter pylori. In contrast, CHIR-090 is arelatively weak competitive and conventional inhibitor (lacking slow, tight-binding kinetics) of LpxC fromRhizobium leguminosarum (Ki=340 nM), a Gram-negative plant endosymbiont that is resistant to thiscompound. An E. coli construct i

6、n which the chromosomal lpxC gene is replaced by R. leguminosarum lpxCis resistant to CHIR-090 up to 100 g/mL, or 400 times above the minimal inhibitory concentration for wild-type E. coli. CHIR-090, a very potent, slow, tight-binding inhibitor of Aquifex aeolicus LpxC, the sequence ofwhich is 31 %

7、identical to E. coli LpxC. CHIR-090 has remarkable antibiotic activity against E. coli and P.aeruginosa, comparable to ciprofloxacin, as judged by disk diffusion assays 1.体内研究 CHIR-090 is a potent antibiotic against E. coli and inhibits E. coli LpxC activity in vitro in the low nM range. E.coli W311

8、0 colonies resistant to 1 g/mL CHIR-090 are not observed without prior chemical mutagenesis. Astrain of E. coli W3110 is able to grow on LB agar plates containing 1 to 10 g/mL CHIR-090, which is 4 to 40times above the MIC of 0.25 g/mL under our conditions for wild-type E. coli W3110. The doubling ti

9、me ofW3110RL is 40 min in the presence of 1 g/mL CHIR-090, which is exactly the same rate as wild-type in theabsence of inhibitor. Wild-type cells stopped growing after about 2 h in the presence of 1 g/mL CHIR-0901.PROTOCOLKinase Assay 1 Disk diffusion is conducted, except that 10 g of each antibiot

10、ic compound is used per filter. Growth in liquidmedium in the presence of CHIR-090 is evaluated as follows: cells from overnight cultures are inoculated into50 mL portions of LB broth at an A600 of 0.02 and grown with shaking at 30C. When the A600 reaches0.15, parallel cultures are treated with eith

11、er 6 L of 500 g/mL CHIR-090 in DMSO or 6 L of DMSO. Toassess cumulative growth, cultures are maintained in log phase growth by 10-fold dilution into pre-warmedmedium, containing the same concentrations of DMSO or DMSO/CHIR-090, whenever the A600 reaches0.4. The minimal inhibitory concentration is de

12、fined as the lowest antibiotic concentration at which nomeasurable bacterial growth is observed in LB medium containing 1% DMSO (v/v), when inoculated at astarting density of A600=0.01. Cultures are incubated with shaking for 24 h at 30C in the presence of CHIR-090. Experiments are performed in trip

13、licate 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nature. 2018 Jul;559(7713):259-263. Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: e02223-16.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Smal

14、l Molecules 您边的抑制剂师www.MedChemE1. Barb AW, et al. Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli.Biochemistry. 2007 Mar 27;46(12):3793-802.2. Barb AW, et al. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligandbinding. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8.3. Tan JH, et al. In Vitro and In Vivo Efficacy of an LpxC Inhibitor, CHIR-090, Alone or Combined with Colistin against Pseudomonasaeruginosa Biofilm. Antimicrob Agents Chemother. 2017 Jun 2