710672C4X Discovery - Validation of GPR142 as a Target for Type II DiabetesClosedGRD Proof of ConceptInnovate UKType-2 diabetes (T2D) affects over 340 million people worldwide, creating an enormous healthcare and socio-economic burden. The GPR142 receptor has been recently suggested as a potential new target for treating T2D with a key advantage: its activation results in insulin secretion as desired but, unlike other targets, it does this only in the presence of high blood sugar levels. Medicines that work through GPR142 should therefore provide marked health benefits over existing T2D therapies, as they will avoid the life-threatening side effect of low blood sugar levels. Moreover, GPR142-based medicines would be orally administered, avoiding the problems caused by injection-based therapies. Poor patient complaince with injectables results in many of the T2D disease symptoms and most of the healthcare and financial burden on the NHS. GPR142-based medicines, if feasible, would therefore not only substantially improve T2D sufferers’ health but also reduce the cost burden on the NHS too. This project aims to carry out vital studies to confirm if GPR142 is indeed the exciting new target for T2D that it promises to be. Very encouraging preliminary literature reports show beneficial effects in clinically relevant acute animal models but, because T2D is a chronic disease, further validation work to assess the chronic effects of GPR142 control is vital to see if it is suitable for safe, long term control. The aim of this project is to perform chronic target validation studies and, if positive, thereby open up a new and better class of T2D medications. If positive, C4X has a head-start in leading this new area, having already designed hit molecules for GPR142 with excellent properties. Positive results would justify a subsequent C4X drug development programme. In time, this would lead to the creation of a new, convenient, safe and effective class of T2D medicines that would have an enormous positive impact on long-term patient health and the economic burden associated with T2D.