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Review
. 2017 Mar 3;61(1):103-114.
doi: 10.1042/EBC20160077. Print 2017 Feb 28.

Polishing the tarnished silver bullet: the quest for new antibiotics

Mark A T Blaskovich  1 , Mark S Butler  2 , Matthew A Cooper  2
Affiliations
Review

Polishing the tarnished silver bullet: the quest for new antibiotics

Mark A T Blaskovich et al. Essays Biochem. .

Abstract

We are facing a potential catastrophe of untreatable bacterial infections, driven by the inexorable rise of extensively drug-resistant bacteria, coupled with a market failure of pharmaceutical and biotech companies to deliver new therapeutic options. While global recognition of the problem is finally apparent, solutions are still a long way from being implemented. In addition to drug stewardship programmes and better diagnostics, new antibiotics are desperately needed. The question remains as to how to achieve this goal. This review will examine the different strategies being applied to discover new antibiotics.

Keywords: Gram negative bacteria; Gram positive bacteria; antibiotic resistance; antibiotics; bacterial infections; drug discovery and design.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Different approaches to discover new antibiotics
Figure 2
Figure 2. Examples of ‘rediscovered’ antibiotics
Figure 3
Figure 3. Approved or late-stage clinical antibiotics that do not obey drug-like rules for oral availability (molecular weight ≤500, H-bond acceptor ≤5, H-bond donor ≤ 5 and log P≤5)
Figure 4
Figure 4. Approved or late-stage clinical antibiotics with ‘undesirable’ chemical functional groups
Figure 5
Figure 5. The CO-ADD screening workflow
Figure 6
Figure 6. Target-based antibiotics
Figure 7
Figure 7. Typical antibiotic drug development pathway
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