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Tuberculosis drug discovery and emerging targets
Author(s) -
Mdluli Khisimuzi,
Kaneko Takushi,
Upton Anna
Publication year - 2014
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12459
Subject(s) - tuberculosis , drug , drug discovery , medicine , intensive care medicine , mycobacterium tuberculosis , extensively drug resistant tuberculosis , bioinformatics , pharmacology , biology , pathology
Current tuberculosis (TB) therapies take too long and the regimens are complex and subject to adverse effects and drug–drug interactions with concomitant medications. The emergence of drug‐resistant TB strains exacerbates the situation. Drug discovery for TB has resurged in recent years, generating compounds (hits) with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead‐optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review proposes strategies for generating improved hits and leads that could help achieve this goal.