Rifalazil  (Synonyms: KRM-1648; ABI-1648)

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: RNA polymerase^[1]

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].

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

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].

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

941.07

Solid

C₅₁H₆₄N₄O₁₃

129791-92-0

CC(C)CN(CC1)CCN1C2=CC(O3)=C(C(O)=C2)N=C(C3=C(NC(/C(C)=C\C=C\[C@@H]([C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@@H]([C@@H]([C@H](/C=C/O[C@@]4(C)O5)OC)C)OC(C)=O)C)=O)C6=O)C7=C6C(O)=C(C)C5=C7C4=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Suchland RJ, et al. Rifalazil pretreatment of mammalian cell cultures prevents subsequent Chlamydia infection.Antimicrob Agents Chemother. 2006 Feb;50(2):439-44.  [Content Brief]

  [2]. Shoen CM, et al. Evaluation of rifalazil in long-term treatment regimens for tuberculosis in mice.Antimicrob Agents Chemother. 2000 Jun;44(6):1458-62.  [Content Brief]

  [3]. Rothstein DM, et al. Development potential of rifalazil.Expert Opin Investig Drugs. 2003 Feb;12(2):255-71.  [Content Brief]