Drug discovery strategies to outer membrane targets in Gram-negative pathogens

Dean G Brown

doi:10.1016/j.bmc.2016.05.004

Drug discovery strategies to outer membrane targets in Gram-negative pathogens

Bioorg Med Chem. 2016 Dec 15;24(24):6320-6331. doi: 10.1016/j.bmc.2016.05.004. Epub 2016 May 5.

Author

Dean G Brown¹

Affiliation

¹ AstraZeneca Neurosciences, Innovative Medicines and Early Development Unit, 141 Portland St., 10th Floor, Cambridge, MA 02139, USA. Electronic address: Dean.brown@astrazeneca.com.

PMID: 27178386
DOI: 10.1016/j.bmc.2016.05.004

Abstract

This review will cover selected recent examples of drug discovery strategies which target the outer membrane (OM) of Gram-negative bacteria either by disruption of outer membrane function or by inhibition of essential gene products necessary for outer membrane assembly. Significant advances in pathway elucidation, structural biology and molecular inhibitor designs have created new opportunities for drug discovery within this target-class space.

Keywords: Antibacterial; Gram-negative; Lipid A; Lipopolysaccharide; Outer membrane.

Publication types

Review

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Bacterial Outer Membrane Proteins / antagonists & inhibitors*
Bacterial Outer Membrane Proteins / genetics
Bacterial Outer Membrane Proteins / metabolism
Drug Discovery*
Gram-Negative Bacteria / drug effects*
Gram-Negative Bacteria / metabolism
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Bacterial Outer Membrane Proteins