Small molecule tools to target glucose metabolism in non-alcoholic fatty liver disease

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The project is aligned to our ongoing efforts to design and synthesise novel chemical biology tool molecules to interrogate and modulate glucokinase enzyme (GK). These chemical probes will be used to establish GK inhibition as a therapeutic target in NAFLD. The project will be split into two complimentary strands which will be approached in parallel: a) the design and synthesis of novel proteolysis targeting chimeric molecules (PROTACs) of GK will test the hypothesis that GK can be targeted for degradation; b) the mapping of GK protein by screening the Newcastle FragLites library will assess GK druggability and establish whether GK inhibition is tractable with a small molecule. The studentship will provide a wealth of experience in medicinal chemistry design and organic synthesis. This would be ideal training for someone wishing to pursue a career in medicinal chemistry or chemical biology.