Rifalazil

Rifalazil (KRM-1648; ABI-1648), a rifamycin derivative, inhibits the bacterial DNA-dependent RNA polymerase and kills bacterial cells by blocking off the β-subunit in RNA polymerase^[1]. Rifalazil (KRM-1648; ABI-1648) is an antibiotic, exhibits high potency against mycobacteria, gram-positive bacteria, Helicobacter pylori, C. pneumoniae and C. trachomatis with MIC values from 0.00025 to 0.0025 μg/ml^[3]. Rifalazil (KRM-1648; ABI-1648) has the potential for the treatment of Chlamydia infection, Clostridium difficile associated diarrhea (CDAD), and tuberculosis (TB)^[2]. IC50 & Target: IC50: RNA polymerase^[1] In Vitro: Rifalazil exhibits antimicrobal activity against Gram-positive enteric bacteria, inhibits Clostridium difficile, Clostridium perfringens, Bacteroides fragilis with MIC₅₀ value of 0.0015, 0.0039, 0.0313 μg/ml, respectively^[3].
Rifalazil exhibits antimicrobal activity against Gram-negative enteric bacteria, inhibits Escherichia coli and Klebsiella pneumoniae with MIC₅₀ value of 16 and 16 μg/ml, respectively^[3].
Rifalazil exhibits antimicrobal activity against non-enteric Gram-positive bacteria, inhibits Methicillin-susceptible Staphylococcus aureus, Methicillin-resistant S. aureus, Methicillin- and quinolone-resistant S. aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae with MIC₅₀ value of 0.0078, 0.0078, 0.0078, 0.0078, 0.0002, 0.0001 μg/ml, respectively^[3].
Rifalazil exhibits antimicrobal activity against Helicobacter pylori, Chlamydia pneumoniae and Chlamydia trachomatis with MIC₅₀ value of 0.004, 0.000125 and 0.00025 μg/ml, respectively^[3].
In Vivo: Rifalazil (oral gavage; 20, 25, and 150 mg/kg; 6-8 weeks) combines with isoniazid (INH) for 6 weeks or greater significantly reduced the number of mice per group in which M. tuberculosis is detected in both spleens and lungs compared to the reductions for the early and late controls. And the addition of Pyrazinamide (PZA) does not significantly improve RLZ-INH therapy at any time point^[2].