Inhibitors of Adipose Triglyceride Lipase (ATGL) for the treatment of Diabetes II and tumor - induced cachexia
University of Graz
The University offers a new technology addressing at least the two markets of tumour-induced cachexia and diabetes type II. Cancer has become a constantly increasing problem and thusabout 1 % of all people in highly developed countries are hit by cachexia, leading to approximately 9 million patients for Europe, Japan and the US. Furthermore, diabetes type II is one of the major lifestyle diseases in the modern world.
Adipose triglyceride lipase (ATGL) is rate-limiting in the degradation of cellular lipid stores. Thus, the enzyme strongly determines the concentration of circulating free fatty acids (FAs) and their availability for energy conversion in tissues. Elevated circu-lating FA concentrations are strongly associated with common metabolic diseases, such as type II diabetes and metabolic syndrome. Mice with genetic deletion of ATGL are resistant to diet-induced diabetes and cancer-associated weight loss (Cancer cachexia). This highlights ATGL as a promising pharmacological target.
Administration of small molecule inhibitors for ATGL leads to a significant reduction in the release of FA from lipid stores in vitro and in vivo. Especially diabetes type II and tumour-induced cachexia are highly relevant targets to be antagonized with these inhibitors. Furthermore, the synthesized compounds allow a tissue specific design that reduces the possibility of drug-related side effects. Results of toxicity analyses have been negative.
- Chemical synthesis of ATGL inhibitors
- Screening for inhibitionof lipolysis in vitro and in vivo
The total market volume estimation for therapy of tumour-induced cachexia is more than one billion US-$. About two million patients related to tumor-induced cachexia in the most important industrial countries are predicted by 2018. Up to now, no approved drugs for tumour-induced cachexia are available WHO estimates 346 million people affected by diabetes type II in 2011. For 2018 about 50 million people are thought to be affected by diabetes type II. Also in China and India the number of patients will increase tremendously to about 50 (India) and 90 (China) million people.
- License agreement
- ownership agreement
- cooperation agreement
Application approved (use in mice in lab)
Status of Patents
- US patent pending
- patent applicatin number
- EP 14705288.0