Journal ArticleDOI
XDR-TB, what is it; how is it treated; and why is therapeutic failure so high?
TLDR
It is important to understand both how resistance emerges as well as the ways in which multi-drug and extensively drug-resistant TB (M/XDR-TB) may be successfully treated.Abstract:
Drug resistance is a major hurdle in the global battle against tuberculosis (TB). In tackling this problem it is important to understand both how resistance emerges as well as the ways in which multi-drug and extensively drug-resistant TB (M/XDR-TB) may be successfully treated. The biggest problem with treatment is the lack of effective drugs. Exciting developments have been made in this area over recent years with useful drugs being found from older agents as well as new discoveries. Patent applications are being made for novel agents and are also possible as new use for older agents such as thioridazine. A flourishing drug pipeline is critical if we are to make progress in the management of M/XDR-TB.read more
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Journal ArticleDOI
Antibiotics from neglected bacterial sources.
TL;DR: A number of antibiotic compounds identified from bacteria of the genera Burkholderia, Clostridium, Lysobacter, Pantoea and Xenorhabdus are reviewed and the potential of organisms and their associated metabolites in future drug discovery efforts are described.
Journal ArticleDOI
Synthesis and Structure−Activity Relationships of Aza- and Diazabiphenyl Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)
Iveta Kmentova,Hamish S. Sutherland,Brian D. Palmer,Adrian Blaser,Scott G. Franzblau,Baojie Wan,Yuehong Wang,Zhenkun Ma,William A. Denny,Andrew M. Thompson +9 more
TL;DR: New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy.
Journal ArticleDOI
Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
Youngchang Kim,Christine Tesar,Joseph Mire,Robert Jedrzejczak,Andrew Binkowski,Gyorgy Babnigg,James C. Sacchettini,Andrzej Joachimiak,Andrzej Joachimiak +8 more
TL;DR: The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-β-lactamase, capable of accommodating many β- lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent β-l lactamase.
Journal ArticleDOI
Exploring Polypharmacology in Drug Discovery and Repurposing Using the CANDO Platform.
Gaurav Chopra,Ram Samudrala +1 more
TL;DR: The CANDO platform is used to analyze and determine the contribution of multitargeting (polypharmacology) to drug repurposing benchmarking accuracy and indicates that a large number of protein structures with diverse fold space and a specific polypharmacological interactome is necessary for accurate drug predictions.
Journal ArticleDOI
Combating Ebola with Repurposed Therapeutics Using the CANDO Platform.
TL;DR: The results indicate that integrating computational docking predictions on a proteomic scale with results from in vitro screening studies may be used to select and prioritize compounds for further in vivo and clinical testing and will significantly reduce the lead time, risk, cost, and resources required to determine efficacious therapies against future EVD outbreaks.
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Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015.
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