BALTIMORE, April 18 /PRNewswire/ -- FASgen, Inc. presented at the AACR meeting in San Diego efficacy and toxicology data on FAS31, FASgen's lead compound for ovarian cancer. FAS31 is an inhibitor of fatty acid synthase (FASi), an enzyme that is highly expressed in many human cancers. Numerous studies have shown that pharmacological FAS inhibition is cytotoxic to a variety of human xenograft models without toxicity. In preliminary toxicity studies, FAS31 showed no observable toxicity in normal tissues in the rat or mouse.
FAS31 inhibits fatty acid synthesis in SKOV3 human ovarian cancer cells in vitro (IC-50 = 6.09 +/- 0.4 ug/ml) at a concentration similar to induce cytotoxicity (LC-50 = 5.2 +/- 2.0 ug/ml). FAS 31 (50 mg/kg/day) for 2 weeks substantially inhibited SKOV3 xenograft growth by >90% compared to vehicle. FAS activity in the treated tumor xenografts was reduced by 82%. This is consistent with published in vitro studies where inhibition of FAS pathway activity by at least 20% led to brisk apoptosis in human cancer cells. No gross or microscopic organ toxicity was identified.
In maximally tolerated dose studies, male and female rats were challenged with increasing single doses of FAS 31 ranging from 0 (vehicle) to 1000 mg/Kg ip or po and followed for 8 days. Aside from one death in the female rats treated with 1000 mg/Kg (ip), no overt toxicity was noted in any other animals; normal motor activity was recorded. In a five-day rat toxicology study, male and female rats were challenged with twice-daily doses of FAS 31 from 0 to 500 mg/Kg ip or orally. No abnormal behavior or distress was noted attributable to FAS 31. All chemistry and hematology studies were within normal limits.
The multiple successful mouse efficacy trials in human ovarian cancer cell lines, showing 80% reduction in SKOV-3 tumor xenografts, and the combination of toxicity, maximum tolerated dose, bioavailability and pK studies lead to the conclusions that FAS31 is efficacious against ovarian cancer tumors, is non-toxic and is a viable pharmacological candidate for anti-cancer therapy.
About FASgen, Inc.: FASgen, Inc. is a drug development company founded in 2000 by four distinguished Johns Hopkins researchers to create new therapeutic products based on the selective inhibition of fatty acid biosynthesis. The Company has the exclusive license from Johns Hopkins to more than 15 years of research in the field, which research continues under a sponsored research agreement with the University.
The Company have has designed and synthesized many compounds that selectively inhibit fatty acid biosynthesis. One group of these compounds holds great promise for new highly specific therapeutics for cancer and the lead compound, FAS31, has demonstrated remarkable efficacy in the reduction in size of tumors in eight different xenograft models, and is in final preparation for starting clinical trials. Additional compounds have the potential of specific therapeutics for obesity and related metabolic disorder. A final group of compounds have the potential of specific therapeutics for TB, including multiple drug resistant TB (MDR-TB) and latent TB infections that
affect one third of the world's population. For more information, visit FASgen's website at http://www.fasgen.com
|SOURCE FASgen, Inc.|
Copyright©2008 PR Newswire.
All rights reserved