FASgen's proprietary compounds provide a totally new approach to the treatment of obesity because they selectively modify food ingestion and reduce body fat while sparing lean tissues.
Over 100 new chemical entities, synthesized using 6 distinct structural scaffolds have been evaluated as a basis for drug development. Selection criteria include reversible inhibition
of fatty acid synthase (FAS), stimulation of carnitine palmitoyl transferase 1 (CPT-1) activity, inhibition of mitochondrial glycerol-3aclytransferase (GPAT), increased rate of fatty
oxidation, lack of cytotoxicity to hypothalamic neurons and other normal cells, lack of mutagenicity, and favorable pharmacologic characteristics such as oral bio-availability.
The most promising compounds have been evaluated in a series of carefully integrated in-vitro experiments using informative cell lines and in-vivo studies in lean and diet induced-obese (DIO) mice,
with special emphasis placed on indirect whole animal calorimetry. These investigations have defined distinct targets and mechanisms by which FASgen's compound produce weigh loss: 1) FAS 267 inhibits
FAS located in the specialized nuclei in the brain stem that control feeding behavior. As a consequence, levels of AMPK fall, the expression of neuropeptide Y (NPY) is reduced and food intake is restricted,
leading to weigh loss; 2) FAS 89B stimulates the activity of CPT-1 in peripheral tissues, leading to an increased rate of fatty acid oxidation and the selective reduction in body fat; 3) FAS 115 acts predominantly by inhibiting GPAT.
In a variety of laboratory animal models of obesity coupled with the characteristic metabolic abnormalities of type II diabetes, studies show that these abnormalities can be corrected as the body weight is reduced to normal.
Compounds discovered by FASgen will be developed in partnership with an established pharmaceutical company in order to reduce the time to market and maximize the potential of these unique entities.