1. Anti-infection
  2. Bacterial

CHIR-090 

Cat. No.: HY-15460 Purity: 98.67%
Data Sheet SDS Handling Instructions

CHIR-090 is a two-step slow, tight-binding inhibitor of Escherichia coli LpxC with Ki of 4 nM.

For research use only. We do not sell to patients.
CHIR-090 Chemical Structure

CHIR-090 Chemical Structure

CAS No. : 728865-23-4

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $176 In-stock
5 mg $160 In-stock
10 mg $260 In-stock
50 mg $950 In-stock
100 mg   Get quote  
200 mg   Get quote  

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    CHIR-090 purchased from MCE. Usage Cited in: Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: e02223-16.

    In vitro efficacy of colistin and CHIR-090 alone or in combination against 3-day-old PAO1 biofilms in biofilm flow cells.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    CHIR-090 is a two-step slow, tight-binding inhibitor of Escherichia coli LpxC with Ki of 4 nM.

    IC50 & Target

    Ki: 4 nM (Escherichia coli LpxC)[1]

    In Vitro

    CHIR-090 is a potent, slow, tight-binding inhibitor of the LpxC deacetylase from the hyperthermophile Aquifex aeolicus, and it has excellent antibiotic activity against P. aeruginosa and E. coli, as judged by disk diffusion assays. 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, including Pseudomonas aeruginosa, Neisseria meningitidis, and Helicobacter pylori. In contrast, CHIR-090 is a relatively weak competitive and conventional inhibitor (lacking slow, tight-binding kinetics) of LpxC from Rhizobium leguminosarum (Ki=340 nM), a Gram-negative plant endosymbiont that is resistant to this compound. An E. coli construct in which the chromosomal lpxC gene is replaced by R. leguminosarum lpxC is resistant to CHIR-090 up to 100 μg/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 of which is 31 % 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].

    In Vivo

    CHIR-090 is a potent antibiotic against E. coli and inhibits E. coli LpxC activity in vitro in the low nM range. E. coli W3110 colonies resistant to 1 μg/mL CHIR-090 are not observed without prior chemical mutagenesis. A strain of E. coli W3110 is able to grow on LB agar plates containing 1 to 10 μg/mL CHIR-090, which is 4 to 40 times above the MIC of 0.25 μg/mL under our conditions for wild-type E. coli W3110. The doubling time of W3110RL is 40 min in the presence of 1 μg/mL CHIR-090, which is exactly the same rate as wild-type in the absence of inhibitor. Wild-type cells stopped growing after about 2 h in the presence of 1 μg/mL CHIR-090[1].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.2858 mL 11.4288 mL 22.8577 mL
    5 mM 0.4572 mL 2.2858 mL 4.5715 mL
    10 mM 0.2286 mL 1.1429 mL 2.2858 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    Disk diffusion is conducted, except that 10 μg of each antibiotic compound is used per filter. Growth in liquid medium in the presence of CHIR-090 is evaluated as follows: cells from overnight cultures are inoculated into 50 mL portions of LB broth at an A600 of 0.02 and grown with shaking at 30°C. When the A600 reaches 0.15, parallel cultures are treated with either 6 μL of 500 μg/mL CHIR-090 in DMSO or 6 μL of DMSO. To assess cumulative growth, cultures are maintained in log phase growth by 10-fold dilution into pre-warmed medium, containing the same concentrations of DMSO or DMSO/CHIR-090, whenever the A600 reaches 0.4. The minimal inhibitory concentration is defined as the lowest antibiotic concentration at which no measurable bacterial growth is observed in LB medium containing 1% DMSO (v/v), when inoculated at a starting density of A600=0.01. Cultures are incubated with shaking for 24 h at 30°C in the presence of CHIR-090. Experiments are performed in triplicate[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    437.49

    Formula

    C₂₄H₂₇N₃O₅

    CAS No.

    728865-23-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 30 mg/mL

    CHIR-090 is prepared in 0.04% DMSO[3].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

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    Product Name:
    CHIR-090
    Cat. No.:
    HY-15460
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