Case Studies

Obesity has been noted as an epidemic in the current American society. Much effort is being placed in education and public awareness to help change lifestyles with further expenditure in drug discovery to seek small molecule therapeutics all along the metabolic syndrome pathway.

Recent history has given rise to a variety of diet regimens as well as “fads” purporting rapid and easy weight loss. One of the most significant and accepted diets today is based primarily on carbohydrate restriction. Studies with diets based on severe caloric restriction or a combination of caloric and carbohydrate restriction have demonstrated not only weight loss but also improved insulin sensitivity.

In an effort to understand the impact of these two diet regimens—severe caloric restriction and severe caloric restriction combined with carbohydrate restriction—the research arm of a large, US-based university worked with Metabolon to create a global biochemical profile to help identify the different impacts of the two diets as well as to identify markers of improved insulin sensitivity.

Gemin X, a pharmaceutical company focused on the discovery and development of advanced oncology therapeutics, approached Metabolon to run a metabolism profile for one of their compounds-GMX1777.

The pro-drug GMX1777, is converted to GMX1778, the active compound which has strong anti-tumor activity in animal and cell culture models, and induces cell death in cells within 48-72 hours in vitro. After initial work performed by Gemin X using genomic, proteomic and biochemical methods, the mechanism of action was still unclear but possible anti-metabolic activity was suggested.

Working with Metabolon's project team, Gemin X designed a simple cell culture time course study to give mechanistic insight into this promising new drug.