Biotech Tracker - Promising Preclinical Studies of New Roche Compounds for Diabetes

BiotechTracker - Promising Preclinical Studies of New Roche Compounds for Diabetes

July 22, 2003 Hoffmann-La Roche (Swiss: ROG) investigators Grimsby and Grippo led an investigative team that have identified a unique class of small molecules that lower blood glucose levels in rodent models of type II diabetes by enhancing both insulin secretion and glycogen storage. Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy was published in the July 18th issue of Science. Related phase I investigation is expected to “be conducted by the end of the year.”

The team describes a class of anti-diabetic agents that activate the enzyme glucokinase such that relevant biological processes augment both liver glucose metabolism and glucose-induced insulin secretion from pancreatic islet cells. This biological activity led to lowered blood glucose levels, improved glucose tolerance test results, and increased liver uptake of circulating glucose in animal models. New drugs resulting from this program have significant potential.

The ability of these glucokinase activators (GKAs) to influence both insulin release and liver glucose metabolism suggests potential development as a monotherapy that impacts two hallmark metabolic processes that are deranged in type diabetes. Grippo comments, “The dual mechanism of action seen with these molecules clearly differentiates them (from other oral antidiabetics agents, such as sulfonylureas).” The agents also have biochemical properties that suggest potential utility as combination agents. The researchers had screened more than 100,000 synthetic compounds for agents that would both activate glucokinase and permit oral administration.

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