AMPK serves as a master switch for cellular energy metabolism and lipid biosynthesis by phosphorylating key enzymes in response to cellular ATP depletion. Agonists of AMPK hold attractive potential as treatments for diabetes and other metabolic disorders, and antagonists are potentially useful in the treatment of breast cancer and certain other lipogenic cancers.
Type 2 diabetes is a disorder of energy storage and metabolism in which the body's tissues exhibit a diminished response to insulin and is unable to maintain blood glucose or lipid levels in the normal range. In more advanced stages of the disease, the demand for higher insulin levels due to increasing insulin resistance often results in the beta cell failure in the pancreas resulting in the need for daily injections of insulin. The end result of persistently elevated serum glucose and lipid levels often leads to cardiovascular disease, blindness, kidney failure, peripheral neuropathy and circulatory problems, including an increased risk of limb amputation due to non-healing wounds.
MTI's lead program is directed toward the discovery of small molecule activators of AMPK, a novel and highly promising target for Type 2 diabetes. AMPK regulates both whole body and cellular energy metabolism by phosphorylating key proteins that control glucose uptake, glycogen mobilization, lipid biosynthesis, and fatty acid metabolism in response to increased intracellular AMP levels. The net effects of AMPK activation at the organism level include an increase in insulin sensitivity, a decrease in gluconeogenesis, free fatty acids, and serum triglycerides.
MTI has in-licensed exclusive rights to AMPK technology from Dartmouth College and has identified multiple novel chemotypes with demonstrated activity in animal models of diet induced Type 2 diabetes. A U.S. patent has recently been filed that claims the structures and applications of multiple active compounds in two lead series. Lead candidates are currently undergoing preclinical pharmacokinetic and toxicology evaluation as clinical development candidates.