title: A medicinal chemists' guide to the unique difficulties of lead optimization for tuberculosis.
abstract: Tuberculosis is a bacterial disease that predominantly affects the lungs and results in extensive tissue pathology. This pathology contributes to the complexity of drug development as it presents discrete microenvironments within which the bacterium resides, often under conditions where replication is limited and intrinsic drug susceptibility is low. This consolidated pathology also results in impaired vascularization that limits access of potential lead molecules to the site of infection. Translating these considerations into a target-product profile to guide lead optimization programs involves implementing unique in vitro and in vivo assays to maximize the likelihood of developing clinically meaningful candidates.
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Newark, NJ, United States.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dartois
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000995:Antitubercular Agents
keywords: Drug discovery; Tuberculosis
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