Stable Analogues of Xenin-25 as Promising Anti-Diabetic Therapies (U318)

Tuesday, 25 October 2016

Ulster University researchers at the Biomedical Sciences Research Institute have identified xenin analogues having a novel mechanism of action with a direct effect on β-cells to release insulinand with GIP potentiating effects. Such peptides could be potentially synergistic or an improvement on existing incretin-based drugs and other oral anti-diabetics for use as novel therapeutics for Type 2 diabetes and obesity.

Problem Being Solved

It is estimated that at least 271 million people are diagnosed with diabetes globally and the World Health Organisation projects this number to reach 423 million by 2030. Therapeutic peptides are one of the most attractive and emerging therapies currently being developed for diabetes due to their numerous advantages over small molecules and/or biologics which include high potency, low toxicity, high specificity, low risk of organ accumulation and drug-drug interaction.


A Proof of Concept funded study has led to the preclinical development of novel, stable analogues based on the native peptide, xenin-25, a K-cell derived gut peptide that is co-secreted with glucose-dependent insulinotropic polypeptide (GIP) following a meal.

Ulster’s lead analogues including, Xenin-25-Gln (K and R substituted with Q) and Xenin-25-[Lys13Pal) (C-16 palmitate linked to ɛ-NH2 group of K13), were generated and evaluated in a comprehensive series of preclinical studies to assess their anti-diabetic potential including examining the longer-term, chronic benefits of repeated daily treatment with these agents in a range of diabetic animal models. Results have identified these xenin analogues as representing potential new therapeutics for the treatment of Type 2 diabetes and obesity.


  •  Novel stable analogues, such as Xenin-25 Gln (K and R substituted with Q) and Xenin-25 GluPal (C-16 palmitate linked to ɛ-NH2 group of K13)
  • New mechanistic approach
  • Direct glucose-lowering and insulinotropic peptide - also potentiates insulin secretory response of GIP
  • Short half-life and rapidly degraded by plasma enzymes
  • Similar performance to exenatide in mouse models
  • Potential synergistic effects with incretins (GIP) and other orals
  • Minimal risk of hypoglycaemia
  • Favourable effect on blood triglycerides
  • Weight neutral
  • May delay the introduction of insulin
  • Promising therapeutic potential in Type 2 diabetes


Gault, Victor, Martin, CM, Flatt, Peter, V, Parthsarathy and Irwin, Nigel (2015) Xenin-25 [Lys(13)PAL]: a novel long-acting acylated analogue of xenin-25 with promising antidiabetic potential. Acta Diabetologica, 52 (3). pp. 461-471.

Martin, Christine M.A., Gault, Victor, McClean, Ste- phen, Flatt, Peter and Irwin, Nigel (2012) Degra- dation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25. Biochemical Pharmacology, 84 (3). pp. 312- 319.

Taylor, Ashley, Irwin, Nigel, McKillop, Aine, Patter- son, Steven, Flatt, Peter and Gault, Victor (2010) Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety. Journal of Endocrinology, 207 (1). pp. 87-93.

Opportunity/Partnership Sought

Ulster University is actively seeking a strategic partner to assist in the further development of this exciting technology, providing a route to market for the safe and effective treatment of obesity and associated type 2 diabetes.

The University is open to a variety of models for collaboration including sponsored research, out-licensing and co-development.  In addition, the inventors of this technology are able to provide valuable know-how in order to assist with its successful commercialisation.

For more information please contact:

Dr Oonagh Lynch

Technology Commercialisation Executive

Research & Impact

Tel: +44 (0) 28 9036 6707

Mob: +44 (0) 77 6536 3191