Dean G. Brown

TL;DR: It is shown that current practices result in overpopulation of certain types of molecular shapes to the exclusion of others using simple PMI plots, which could help catalyze improvements in integration of new synthetic methodologies as well as new library design.

TL;DR: Findings from target-based and phenotypic screening efforts carried out at AstraZeneca over the past decade are described, some of the subsequent chemistry challenges are discussed and a description of new approaches comprising a combination of computational modelling and advanced biological tools which may pave the way towards the discovery of new antibacterial agents are described.

TL;DR: Opportunities for the expansion of the medicinal chemists' synthetic toolbox are highlighted to enable enhanced impact of new methodologies in future drug discovery.

TL;DR: The evolution of the approach to target validation, hit and lead optimization, pharmacokinetic/pharmacodynamic modelling and drug safety testing, which have helped improve the quality of candidate drug nomination, as well as the development of the right culture.

TL;DR: Physical properties of antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found from high throughput screens conducted on both biochemical and phenotypic bacterial targets and illustrated that compounds least susceptible to efflux were those which were highly polar and small in MW or very large and typically zwitterionic.