KKL-55 

KKL-55 is a broad-spectrum antibacterial agent that inhibits the trans-translation pathway and the ClpXP protease. KKL-55 suppresses trans-translation of non-stop mRNA, interferes with the binding of EF-Tu to tmRNA, and inhibits the proteolysis of substrates by ClpXP. KKL-55 blocks spore germination of Bacillus anthracis and protects macrophages from damage induced by anthrax toxin. By virtue of its inhibitory effect on ClpXP, KKL-55 synergistically enhances the antibacterial activity of antibiotics against drug-resistant Staphylococcus aureus. KKL-55 can be used in studies related to bacterial infections^[1][2][3].

KKL-55 potently inhibits and kills Bacillus anthracis Sterne vegetative cells in vitro, with an MIC of 6.6 μg/mL, IC₅₀ of 4.8 μg/mL, and bactericidal activity at 13.3 μg/mL^[1].
KKL-55 (1.7-13.3 μg/mL; 24 h) completely inhibits germination of Bacillus anthracis Sterne spores at 1.2× MIC (8.0 μg/mL) and kills spores at 2× MIC (13.3 μg/mL) in vitro, with lasting inhibitory effects after drug removal^[1].
KKL-55 (3.3-26.6 μg/mL; 9-18 h) protects RAW 264.7 macrophages from Bacillus anthracis Sterne spore-induced death with an IC₅₀ of 5.7 μg/mL, achieves complete protection at 4× MIC (26.6 μg/mL)^[1].
KKL-55 (compound F2) (10 μM) inhibits trans-translation in Escherichia coli expressing luc-trpAt^[3].
KKL-55 (100 μM) inhibits both trans-translation tagging and proteolysis of tagged proteins in Escherichia coli, as shown by increased fluorescence in both mCherry-trpAt and mCherry-tag reporter strains at 100 μM^[3].
KKL-55 directly inhibits tmRNA-mediated trans-translation tagging in an Escherichia coli-based in vitro coupled transcription/translation system^[3].
KKL-55 has broad-spectrum antibacterial activity, with bacteriostatic effects on Shigella flexneri, Bacillus anthracis, Escherichia coli ΔtolC, and Escherichia coli ΔtolC ΔssrA, and bactericidal effects on Mycobacterium smegmatis at its MIC of 25 μM^[3].
KKL-55 (100 μM; 5-20 min) inhibits ClpXP protease activity in Escherichia coli, increasing the half-life of the ClpXP substrate GFP-AA from 5.4 min to 18.7 min at 100 μM^[3].
KKL-55 (15-40 μM; 24 h) synergistically enhances the antibacterial activity of penicillin against Bacillus anthracis Sterne and daptomycin against MRSA, and reduces daptomycin resistance in daptomycin-nonsusceptible MRSA strains at concentrations of 15-40 μM over 24 h^[3].
KKL-55 (10 μM; 24 h) inhibits proteolysis of tagged mCherry-LAA in Mycobacterium smegmatis LEC282^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

265.70

C₁₁H₁₂ClN₅O

639048-45-6

O=C(C1=CC(Cl)=CC=C1)NC2=NN=NN2CCC

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Alumasa JN, et al. Tetrazole-Based trans-Translation Inhibitors Kill Bacillus anthracis Spores To Protect Host Cells. Antimicrob Agents Chemother. 2017;61(10):e01199-17. Published 2017 Sep 22.  [Content Brief]

  [2]. Varshney, et al. A trans -translation inhibitor kills Mycobacterium tuberculosis by targeting ribosomal protein bL12. bioRxiv [Preprint]. 2025 Jun 2:2025.06.02.656638.

  [3]. Ramadoss NS. The trans-translation pathway as a target for broad-spectrum antibacterial development. 2013.