CHIR-090

Research use only, not for human use.

CHIR-090 is a very potent and selective LpxC inhibitor with antibiotic activity.

CHIR-090 is a very potent and selective LpxC inhibitor. CHIR-090 has excellent antibiotic activity against Pseudomonas aeruginosa and Escherichia coli. CHIR-090 is also a two-step slow, tight-binding inhibitor of E. coli LpxC with Ki = 4.0 nM, Ki* = 0.5 nM, k5 = 1.9 min-1, and k6 = 0.18 min-1. CHIR-090 at low nanomolar levels inhibits LpxC orthologues from diverse Gram-negative pathogens, including P. 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. CHIR-090 is an excellent lead for the further development of new antibiotics targeting the lipid A pathway.

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.

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.

CHIR-090 | CHIR 090 | CHIR090

Others

Other Targets

Escherichia coli LpxC

Infection

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728865-23-4

437.19

C24H27N3O5

>98% (HPLC)

DMSO : ≥ 30 mg/mL; 68.57 mM

ONC(=O)[C@@H](NC(=O)c1ccc(cc1)C#Cc1ccc(cc1)CN1CCOCC1)[C@@H](C)O

N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-[2-[4-(morpholin-4-ylmethyl)phenyl]ethynyl]benzamide

(-20℃)

With Ice Pack

≥ 2 years