Discovery Partnerships with Academia (DPAc) was established in late 2010 as a new mechanism to combine disease insight from the academic community with GSK’s drug discovery engine in order to translate academic innovative ideas into medicines that meet the needs of patients. The collaboration with Mr Damian Mole, Clinical Senior Lecturer and Honorary Consultant Surgeon, at The University of Edinburgh was one of the first DPAc collaborations to be established. Damian’s work uncovered a novel link between 3-hydroxykynurenine (3HK), a tryptophan metabolite, and the development of severe acute pancreatitis suggesting that inhibition of the enzyme responsible for the generation of 3HK, kynurenine monooxygenase (KMO), could represent a revolutionary new approach to the treatment of acute pancreatitis.<br/> <br/>The presentation will describe the medicinal chemistry strategy which utilised substrate knowledge to discover KMO inhibitors with the required properties commensurate with intravenous dosing.  Low molecular weight inhibitors with excellent aqueous solubility were rapidly identified and shown to have a clear protective effect in a rat model of acute pancreatitis when dosed therapeutically. Subsequent structural knowledge enabled the fine tuning of key interactions with the protein and ultimately led to the identification of the development candidate, a highly potent and selective KMO inhibitor with outstanding physicochemical properties.<br/>

Disclosure of a development candidate to treat severe acute pancreatitis through a drug discovery partnership between GlaxoSmithKline and the University of Edinburgh

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.