fungal systems pharmacology

The single biggest reason why first-in-class drug projects fail is due to invalid targets. Often, drug discovery projects make up their mind a target should work and then generate evidence to support it. However, the evidence often only provides necessary but insufficient proof for how the target might work. This is frequently overlooked as all eyes are on the compound. This approach is biased and risky.

Instead, we believe there is insufficient work performed to invalidate targets. A target may only be qualified after it is rigorously tested under diverse conditions. Clarity for when a target may work is crucial. We also need to critically evaluate the minimum degree and duration of target engagement that are needed for drug discovery. This helps set the target compound profile.

Using literature data, we developed a model to link doses of an oxidative stress agent with cytostatic and cytotoxic effects in Candida albicans. We are performing new experiments to investigate how target engagement leads to efficacy. The target engagement biomarkers will be incorporated into our model.

Collaborators: Paraskevi Kritsiligkou, Janet Quinn (Newcastle), Elaine Bignell (Exeter)

PhD student: Ivan Ibanda