Novel Human α-Amylase Inhibitors
Diabetes and obesity control by modulation of human-pancreatic α-amylase (HPA) activity. Potent tight binding competitive inhibitors of HPA with Ki values below 10 nM have been identified.
- Improved diabetes and obesity control.
- Effective control of post-prandial glucose levels with less side effects.
- Selective inhibition of Human-pancreatic α-amylase over other glycosidases reduces the gastrointestinal side-effects.
- Ki values < 10nM
Researchers at UBC have identified small molecule and peptidic potent Human pancreatic α-amylase (HPA) inhibitors for use in the treatment of diabetes and obesity. Detailed kinetic analysis revealed the active agents to be tight binding competitive inhibitors of HPA with Ki values below 10 nM.
HPA is a key enzyme in the digestive system, catalyzing the initial step in the hydrolysis of starch, a principal source of glucose in the diet. Diabetes and obesity can be controlled by modulating HPA activity through the therapeutic use of inhibitors. The incidence of diabetes and obesity is increasing at an alarming rate, with diabetes alone afflicting 6% of the population throughout the Western World and ranking as the third most prevalent disease.
Although two α-glucosidase inhibitors, acarbose (Precose) and miglitol (Glyset) are currently in medical use, their effectiveness is limited by deleterious side-effects due to the non-specific glycosidase inhibition. New and more effective drugs, which can target HPA specifically, with longer-term effects and lower systemic availability will be valuable tools to control these conditions.
Two HPA inhibitors in this technology have shown a high level of selectivity towards HPA when tested against a series of other glycosidases, a highly desirable attribute for any potential HPA-targeted therapeutic because the increased specificity reduces the unwanted side-effects.