Cyclis Pharmaceuticals reports studies defining new mechanism for potential cancer therapies

The findings are published in the on-line edition of the Proceedings of the National Academy of Sciences.

"When DNA damage occurs in normal cells, a checkpoint pathway is activated that triggers apoptosis when that damage cannot be repaired," said Cyclis Vice President of Research Dr. Chiang J. Li, senior author of the paper. "In cancer cells these pathways are defective, leading to uncontrolled growth. These studies strongly suggest that one such pathway, involving the E2F1 protein, can be turned on with small molecule drugs, leading to selective killing of cancer cells."

"This research details one example of how our ACT TM platform works at the molecular level," said Cyclis President and CEO, Dr. Samuel K. Ackerman. "We have applied this platform successfully with our initial drug candidates. This approach also opens the door to additional drug discovery for a wide range of cancers by applying knowledge of this unique mechanism of action to multiple drug targets of the checkpoint system."

In these studies, the researchers compared the effects of ß-lapachone on human cancer cell and normal cell survival. They demonstrated that the compound selectively induces apoptosis in the tumor cells, but not in normal cells. They further showed that ß-lapachone-treated cancer cells, but not normal cells, exhibit elevated E2F1 protein levels, indicating activation of a specific checkpoint apoptosis pathway. Prior published research by Dr. Li and colleagues has demonstrated the effectiveness of ß-lapachone in animal models.

In addition to Dr. Li, other authors on the paper were Youzhi Li, Ph.D., Xiangao Sun, Ph.D., both of whom are now at Cyclis, and Arthur Pardee, Ph.D., Professor Emeritus at the Dana-Farber Cancer Institute and a member of the Cyclis Scientific Advisory Board.

About Cyclis Pharmaceuticals, Inc.
Cyclis Pharmaceuticals, Inc., a privately held biopharmaceutical company headquartered in Norwood, MA, is engaged in the discovery and development of novel drugs for the treatment of cancer based on the restoration and activation of cellular checkpoints. The Company's unique approach, Activated Checkpoint Therapy TM (ACT TM ), is an innovative form of targeted therapy that offers the potential for improved efficacy and reduced toxicity over other molecular approaches and traditional cancer chemotherapy. Cyclis' proprietary discovery programs target major pathways controlling checkpoints and apoptosis. Cyclis' first proprietary candidate, CO-501, is scheduled to begin clinical trials for the treatment of solid and hematologic tumors in mid-2003. For more information, visit Cyclis' website at www.cyclispharma.com .

Proceedings of the National Academy of Sciences