Modified Cholecystokinin (CCK-8) Analogues for Treatment of Obesity and/or Type 2 Diabetes
Cholecystokinin (CCK) is a neuropeptide hormone found in the brain and secreted from gut endrocrine cells that was originally identified by its ability to stimulate gall bladder contraction. CCK is known to play a significant role in many physiological processes, including regulation of feeding and insulin secretion.
CCK exists in multiple molecular forms and the COOH-terminal octapeptide, CCK-8, is well conserved between species and is the smallest form that retains its full range of biological activities. The short action of CCK combined with rapid loss of efficacy of small molecule agonists when chronically administered remains an obstacle in the exploitation of its potential for body weight management.
Research from the University of Ulster has shown that N-terminally modified CCK-8 analogues possess an enhanced ability to reduce voluntary food intake and body weightwhen compared with native CCK-8 with an extended duration of action and efficacy in a variety of animal models. In addition, these effects have been associated with notable improvements of blood glucose control, positioning these peptides as a novel class of antiobesity agents with additional antidiabetic actions.
· Peptide analogues are resistant to aminopeptidase degradation, demonstrate increased and long lasting biological activity compared with native CCK-8 and are not associated with desensitization.
· Stable, modified peptide analogues are suitable for chronic administration with in vivo studies demonstrating twice daily dosing to result in substantial body weight loss over a period of more than 40 days. These effects are associated with significant decrease of non-fasting glucose, lower glycaemic excursion following feeding, improved glucose tolerance and enhanced insulin sensitivity.
· Analogues can be used alone or in combination with incretin mimetics and other agents, with research showing synergistic benefits.
· External CRO studies in the U.S. have shown significant body weight reduction comparable with sibutramine which was free from adverse effects on the pancreas, liver, kidney and muscle.
Jennifer Cook: firstname.lastname@example.org / +44 (0) 2890 366 705