100989 – A monomeric peptide multi-agonist targeting the GLP1 receptor and NPY receptors for weight loss and glucoregulation

  • Target to produce potent weight-loss
  • Reduced incidence of gastric disturbance and malaise
  • Fights obesity and diabetes


A series of chimeric peptides that provide a mechanism for obesity treatment concomitantwith T2DM in the form of dual agonism of the anorectic neuropeptide Y-receptor (Y2-R) and theglucoregulatory receptor GLP1-R. Preliminary results show that, dependent on the selectedpeptide, once-daily administration suppress FI in male and female rats can be reduced to 12-65%compared to baseline conditions before treatment, dependent on dose and age of animals, andglucose tolerance can be improved as well. Peptides also demonstrated Y1-receptor agonism,conferring protection on beta-islet cells against inflammatory damage. The peptides weredesigned by targeting serial anorectic pathways simultaneously and are promising candidates formodulating FI and glucoregulation in an efficacious and safe way.


Glucagon-like peptide-1 receptor agonists (GLP1RAs), are potent stimulators of glucose-dependentinsulin secretion which also modulate satiety and energy intake. Treatment with a GLP-1RAaddresses central inhibition of appetite. Few treatments for type 2 diabetes (T2D) and obesity achievemeaningful long-term weight-loss, however, and, importantly, the hypophagic effects of all knownGLP-1RAs are accompanied by nausea and vomiting (affecting ~20-50% of patients),20 leading todiscontinuation of drug treatment in ~6-10% and reduced dose tolerance in another ~15% of patients.This effect manifests to also limit the use of GLP1-RA to treat T2DM in lean patients due to comorbiditiessuch as cystic fibrosis, cancer, HIV, amongst others. New treatments based on dualagonists of GLP1-R/Glucagon receptor (GlucR) also display such issues, many including additionalgastrointestinal issues such as distention, diarrhea, etc. Thus, there is a critical need for a newgeneration of obesity medications that provide glycemic control with enhanced hypophagic responsewithout nausea/emesis. Another unmet need in the treatment of T2DM is protection against β-isletcell mass loss, associated with the cytokine storm evident in diabetes.

Potential Applications

The technology will combine targeting to produce potent weight-loss, maintain β-cell mass, withreduced incidence of gastric disturbance and malaise.

Contact Information

Name: Jennifer Crisp

Email: jmcrisp@syr.edu

Phone: 315-443-5196