Key targets and relevant inhibitors for the drug discovery of tuberculosis.

Abstract:

:Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year. An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can treat both drug-sensitive and resistant TB infections. M. tuberculosis evades the host immune system and drug regimes by entering dormant phase within macrophage. As a consequence, there is a pressing need for new vaccines and antimicrobials to treat persistent infections. As clinically used antibiotics target very few essential functions of mycobacterium, it is rational that identification of new targets that are essential for bacterial growth and survival can serve as starting point for designing of novel drugs to cure both drug-sensitive and resistant TB infections. With the development of molecular biology and structural biology and the availability of the genome sequence of M. tuberculosis, some success has been achieved in the identification of new targets in M. tuberculosis and their relevant inhibitors. This review summarizes about ninety important targets that participate in a range of diverse physiological processes in M. tuberculosis and seven new drugs currently in clinical phase 2 or 3 trials. In addition, promising inhibitors with novel mechanisms of action and clinical vaccine candidates are highlighted.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Xiong X,Xu Z,Yang Z,Liu Y,Wang D,Dong M,Parker EJ,Zhu W

doi

10.2174/1389450111314060009

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

676-99

issue

6

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-20130402-3

journal_volume

14

pub_type

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