Development of Fungal-selective Yck2 Inhibitors to Combat Drug-resistant Invasive Fungal Diseases

Invasive fungal infections represent a major threat to human health that is exacerbated by the widespread emergence of antifungal drug resistance. Existing therapies are already limited in number, largely due to the similarity between fungal and human cells. As such, new antifungal approaches are urgently needed to combat drug-resistant fungal pathogens. We have previously implicated key fungal stress response regulators in the development of drug resistance, including the protein kinase Yck2. Moreover, we have identified chemical scaffolds active against this promising target which reverse resistance to clinical antifungals. The goal of this research project is to develop molecules that selectively inhibit fungal Yck2. We will leverage a structure-guided approach to generate novel Yck2 inhibitors and assess their target engagement, bioactivity and mammalian toxicity as antifungal potentiators and as single agents. This work has the potential to empower mechanistically novel strategies in the treatment of invasive fungal diseases.

Faculty Supervisor:

Justin Nodwell

Student:

Partner:

Bright Angel Therapeutics

Discipline:

Life Sciences

Sector:

Professional, scientific and technical services

University:

University of Toronto

Program: