MAC-545496

Research use only, not for human use.

MAC-545496 is a glycopeptide-resistance-associated protein R (GraR) inhibitor, is an antivirulence agent.

MAC-545496 is a glycopeptide-resistance-associated protein R (GraR) inhibitor, is an antivirulence agent. MAC-545496 could also serve as an antivirulence agent alone; it attenuates MRSA virulence in Galleria mellonella larvae. MAC-545496 inhibits biofilm formation and abrogates intracellular survival in macrophages. Mechanistic characterization revealed MAC-545496 to be a nanomolar inhibitor of GraR, a regulator that responds to cell-envelope stress and is an important virulence factor and determinant of antibiotic resistance.

MAC-545496 potently synergizes with Cefuroxime; concentrations as low as 0.03 μg/mL (~75 nM) lowers the β-lactam MIC from 512 to 8 μg/mL against S. aureus USA300. MAC545496 also synergizes with Cefuroxime and Oxacillin against a collection of ten S. aureus clinical isolates. In addition, MAC-545496 potentiates the effect of Cefuroxime against representatives of other circulating MRSA strains such as USA100, USA400 and USA500 to different extents, with the exception of CMRSA4, a USA200/EMRSA16 isolate. MAC-545496 also synergizes with the antimicrobial peptides colistin and polymyxin B.MAC-545496 shows inhibition of mprF expression in a concentration-dependent manner; the IC50 value is 0.0376 μg/mL. MAC-545496 also inhibits the citrateinduced biofilm formation in the wild type in a concentration dependent manner.

In vivo, MAC-545496 is effective as a monotherapy for MRSA infected Galleria mellonella larvae. MAC-545496 activity is evidenced by increased survival of the drug-treated larvae as compared to infected untreated ones. This corresponded to concentration-dependent killing of S. aureus in the hemolymph of the larvae observed from the CFUs recovered from the hemolymph 200 min after infection. Treatment of S. aureus-infected larvae with MAC-545496 occurred 30min after infection that mimics acquiring bacterial infection before initiating antimicrobial therapy .

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Others

Other Targets

Glycopeptide-resistance-associated protein R (GraR)

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838810-96-1

419.89

C18H18ClN5O3S

>98% (HPLC)

DMSO:250 mg/mL (595.39 mM; Need ultrasonic)

[O-][N+](=O)c1cc(ccc1N1CCCCC1)C(=O)NC(=S)Nc1ccc(Cl)cn1

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(-20℃)

With Ice Pack

≥ 2 years