title: New agents for the treatment of drug-resistant Mycobacterium tuberculosis.
abstract: Inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (MDR-TB). Treatment of MDR-TB infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. This review focuses on emerging drug classes that have the potential for treating MDR-TB and highlights their particular strengths as leads including their mode of action, in vivo efficacy, and key medicinal chemistry properties. Examples include the newly approved drugs bedaquiline and delaminid, and other agents in clinical and late preclinical development pipeline for the treatment of MDR-TB. Herein, we discuss the challenges to developing drugs to treat tuberculosis and how the field has adapted to these difficulties, with an emphasis on drug discovery approaches that might produce more effective agents and treatment regimens.
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Pharmaceutical Sciences Graduate Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Hoagland
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jiuyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Lee
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: richard.lee@stjude.org.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lee
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D009169:Mycobacterium tuberculosis; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: Antibiotic; Antituberculosis; Bedaquiline (PubChem CID: 5388906); Delamanid (PubChem CID: 6480466); Drug discovery; Faropenem (PubChem CID: 65894); Lee1599 (PubChem CID: 60173108); PBTZ 169 (PubChem CID: 57331386); Q203 (PubChem CID: 68234908); SQ109 (PubChem CID: 5274428); SQ641 (PubChem CID: 3013049); Sutezolid (PubChem CID: 465951); TCA 1 (PubChem CID: 4557640); Tuberculosis