Description: AFN-1252 tosylate monohydrate (API-1252; AFN-12520000; Debio-1452) is a novel and potent inhibitor of enoyl-(acyl-carrier protein) reductase Fabl with the potential for the treatment of acute bacterial skin. AFN-1252 exhibits typical MIC(90) values of ≤0·015 μg/ml against diverse clinical isolates of S. aureus, orally bioavailable absorption, long elimination half-live and efficacy in animal models. AFN-1252 displays a Staphylococcus-specific spectrum of activity.
References:
[1]. Karlowsky JA, et al. AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity. Antimicrob Agents Chemother. 2009 Aug;53(8):3544-8.
[2]. Narasimha Rao K, et al. AFN-1252 is a potent inhibitor of enoyl-ACP reductase from Burkholderia pseudomallei-Crystal structure, mode of action, and biological activity. Protein Sci. 2015 May;24(5):832-40.
[3]. Yao J, et al. Resistance to AFN-1252 arises from missense mutations in Staphylococcus aureus enoyl-acyl carrier protein reductase (FabI). J Biol Chem. 2013 Dec 20;288(51):36261-71.
[4]. Parsons JB, et al. Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252. Antimicrob Agents Chemother. 2013 May;57(5):2182-90.
[5]. Yao J, Ericson ME, Frank MW, Rock CO. Enoyl-Acyl Carrier Protein Reductase I (FabI) is Essential for the Intracellular Growth of Listeria monocytogenes. Infect Immun. 2016 Oct 10. pii: IAI.00647-16. PubMed PMID: 27736774.
Related CAS: 620175-39-5 (free base); 1047981-30-5 (tosylate monohydrate); 1047981-31-6 (tosylate)