Technology Overview

Researchers at Durham have developed low molecular weight antimicrobials designed to target the cell membrane. Their mode of action is novel (and different from other membrane-targeting actives such as antimicrobial peptides).

The USP lies in the mode of action (novel and unexploited). The agents modify the chemical composition of the membrane and do not target any metabolic pathways. Membranes are an interesting target – they are ubiquitous in bacteria, and also found in enveloped viruses (such as Ebola). These agents therefore have the potential to be tuned for either broad or narrow spectrum activity. The agents are “pharma-friendly”, i.e. acceptable by Lipinski rules.

The mode of action exploits chemical processes that the researchers have identified, whereby some functional groups are reactive towards chemical components of the membrane, leading to their chemical transformation within the membrane. This transformation can be detrimental to cell viability. There is chemical selectivity within this process (some functional groups are reactive, others are not). The researchers are undertaking research to establish a framework for understanding the reactivity (at an academic level). At an application level, the researchers have screened ~80 compounds to date for this activity. Screens have been conducted in vitro (using liposome models) and in vivo using a small selection of G+ and G- organisms, as well as screening for adverse activity using hemolysis assays. Given that the researchers have only tested a small number of compounds, initial results are encouraging – they have a handful of compounds that have acceptable activity in microorganisms (with MICs of 10–100 micromolar, ) and low activity in hemolysis assays.

Opportunity

The researchers aim to protect and exploit the novelty in these compounds, but in the short to medium term would really benefit from the involvement of an industrial partner to expand screening and provide access to additional resources (software (QSAR), expertise (QSAR), existing compound libraries)).

Novel Membrane Targeting Anti-microbials

IP Status

Seeking