Iclaprim (AR100; RO482622)

Description: Iclaprim (formerly known as AR-100 and RO-482622) is a novel diaminopyrimidine, and a selective inhibitor of dihydrofolate reductase which can inhibit the growth of S. aureus (MRSA) with an MIC90 of 0.06 ug/mL. It has shown potent, extended-spectrum in vitro activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and vancomycin-resistant S. aureus and macrolide-, quinolone- and trimethoprim-resistant strains. In addition, iclaprim has demonstrated activity against Streptococcus pneumoniae including penicillin-, erythromycin-, levofloxacin- and trimethoprim/sulfamethoxazole-resistant strains. Furthermore, in vitro activity has also been observed against Gram-negative bacteria and atypical bacteria. The pharmaco-kinetic profile of this agent reveals that iclaprim is available for intravenous and oral use, with good oral bioavailability. Phase II clinical trials have shown promise in its use for complicated skin and skin structure infections that are caused by methicillin-resistant S. aureus and two Phase III clinical trials have been recently completed for the same indication. Phase II trials evaluating the efficacy in respiratory infections are expected to start in 2007. At this early point in clinical development, the available reported data indicate potential for iclaprim as a new antibiotic for parenteral and oral treatment of complicated skin and skin structure infections.

References: Expert Opin Investig Drugs. 2007 Sep; 16(9):1441-8; Bioorg Med Chem Lett. 2003 Dec 1; 13(23):4217-21.

Related CAS: 192314-93-5 (free base); 474793-41-4 (mesylate salt)