An industry-academia collaboration has been initiated to commercialise newly discovered compounds which hold potential for a new way of treating patients with advanced diabetes type 2.
Professor Per Kjellbom, Lund University, with Dr Michael Rützler, Lund University, as principal investigator and Professor Søren Nielsen, Aalborg University, have identified a novel mechanism for inhibiting hepatic glucose production. Especially patients with deteriorating kidney function, for which the use of currently available oral therapies is precluded, are expected to benefit from such treatment option.
Initially, the academic researchers studied the role of a specific protein in the liver focusing to elucidate its function. They found that the activity of this liver cell protein contributes to the amount of glucose in blood. The results from these studies led to the idea to use inhibitors to reduce glucose output from the liver, a mechanism dysregulated in diabetes patients. Studies in knock-out mice lend support to this notion, demonstrating a high potential for developing a novel therapy for diabetes.
Further studies employing cell systems led to the discovery of synthetic compounds that had the desired effect, acting as inhibitors of the protein, but these compounds were not suitable for further development into a therapy. Lund University Innovation systems supported the research group by connecting them with a private company, Red Glead Discovery, (based at Medicon Village in Lund) to set up plans for generating first-in-class inhibitors fit for commercialisation. The aim is to out-license lead compounds to Pharma partners looking for novel targets for treatment of diabetes.
The chemists at Red Glead Discovery, drawing on their knowledge and competence from industrial drug discovery projects within Pharma, synthesised a series of drug-like inhibitors which demonstrated effects on whole body glucose production after a single administration in diabetic mice. However, despite having reached proof of mechanism, compound properties will need to get improved, in order to fulfil the criteria for further development by Pharma companies. The next milestone in the project is to improve these compounds by increasing solubility using rational design and possibly also to reduce plasma protein binding, while retaining IC50 < 30 nM,
Thus, this grant will support a medicinal chemistry program for generation of improved inhibitors that can enter preclinical testing.