title: The oxazolidinones: past, present, and future.
abstract: The success of linezolid stimulated significant efforts to discover new agents in the oxazolidinone class. Over a dozen oxazolidinones have reached the clinic, but many were discontinued due to lack of differentiated potency, inadequate pharmacokinetics, and safety risks that included myelosuppression. Four oxazolidinones are currently undergoing clinical evaluation. The Trius Therapeutics compound tedizolid phosphate (formerly known as torezolid phosphate, TR-701, DA-7218), the most advanced, is in phase 3 clinical trials for acute bacterial skin and skin structure infections. Rib-X completed two phase 2 studies for radezolid (Rx-01_667, RX-1741) in uncomplicated skin and skin structure infections and community-acquired pneumonia. Pfizer and AstraZeneca have each identified antitubercular compounds that have completed phase 1 studies: sutezolid (PNU-100480, PF-02341272) and AZD5847 (AZD2563), respectively. The oxazolidinones share a relatively low frequency of resistance largely due to the requirement of mutations in 23S ribosomal RNA genes. However, maintaining potency against strains carrying the mobile cfr gene poses a challenge for the oxazolidinone class, as well as other 50S ribosome inhibitors that target the peptidyl transferase center.
authors.affiliation: Trius Therapeutics, Inc., Department of Biology, San Diego, California 92121, USA. kshaw@triusrx.com
authors.forename: Karen Joy
authors.initials: KJ
authors.lastname: Shaw
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barbachyn
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000266:history / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D002986:Clinical Trials as Topic; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009154:Mutation; D023303:Oxazolidinones / Q000737:chemistry / Q000266:history / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones