Challenges of Antibacterial Discovery
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TLDR
The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.Abstract:
Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.read more
Citations
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Antibiotics and Bacterial Resistance in the 21st Century
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References
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Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
TL;DR: This review summarizes the development in the field since the previous review and begins to understand how this bilayer of the outer membrane can retard the entry of lipophilic compounds, owing to increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopoly Saccharide structure is modified by environmental conditions.
Journal ArticleDOI
Mutations of bacteria from virus sensitivity to virus resistance
Salvador E. Luria,Max Delbrück +1 more
TL;DR: This article reported Luria and Delbruck's breakthrough study in which they established that viruses do not induce mutations in bacteria, but that virus-resisting mutations are spontaneous.
Journal ArticleDOI
New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays
TL;DR: A number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens are described.
Patent
High throughput screen
TL;DR: In this paper, a high throughput screen for determining the effect of test compounds on ion channel or transporter activity was proposed, and a method for monitoring ion channel activity in a membrane.
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