press release archive

Rigel Identifies Novel Gene that Mediates Cellular Functions that can Lead to Cancer and Inflammatory Disease

Findings Published in Current Biology

South San Francisco, CA - May 27, 1999

Rigel, Inc., a drug discovery and development company, today announced that it has identified a new novel gene, RIP-3, that can mediate key biological functions that can cause a cellular progression to cancer and inflammatory diseases. The findings, which were uncovered using Rigel's proprietary, high-throughput two-hybrid screening technology, are published in the current issue of the peer-reviewed journal Current Biology.

The researchers found that RIP-3, a TNF (tumor necrosis factor) signaling pathway member that had not been previously identified, can activate apoptosis, a cellular function that leads to programmed cell death and may be useful as a method of killing cancer cells, and NF-kB, a key transcription factor that regulates the expression of many inflammatory response genes. The discovery of RIP-3 will enable Rigel to further develop small molecules that can regulate these disease pathways.

The RIP-3 discovery was made using Rigel's two-hybrid technology, which is able to very rapidly screen very large quantities of genes of interest to determine which ones elicit biochemical interactions that cause desired changes within the context of the complete cell signaling pathway. Using this highly-sensitive technology that is able to identify genes that go undetected using conventional two-hybrid technology, scientists can discover and validate important therapeutic targets within a period of six months, instead of years as with traditional approaches. In the past 12 months alone, Rigel scientists have been able to identify thousands of proteins and the genes that produce them, including the RIP-3 gene, and have built extensive, functionally-relevant cellular signaling pathway databases.

"We are very excited about these findings," said Donald Payan, MD, Chief Scientific Officer and co-founder of Rigel, Inc. "They not only represent further validation of our two-hybrid screening technology, but they represent an interesting new window into this area of biology and therefore, into the development of drugs for cancer and inflammatory diseases."

Rigel's core technologies use large libraries of retrovirally delivered peptide or protein probes to find potential drug targets within cells of interest (e.g. tumor cells) that cause beneficial functional changes (e.g. reversal of cancerous mutations in tumor cells). The resulting "target-probe pair" is a critical first step in designing a drug that can provide the equivalent beneficial effect in patients. In addition to starting with large scale screens of unknown areas of the cells to find these pairs, Rigel can use such insights into the intracellular signaling of these cells (such as RIP-3) to focus its search for the optimal target-probe pair. Probes that interact with such discovered molecules and which then cause functional changes in subsequent biology screens can identify drug targets.

Rigel, Inc., a privately held company founded in 1997, is focused on the discovery of novel therapeutic agents. The Company's rapid drug target identification and validation technology integrates proprietary advances in gene transfer techniques with combinatorial chemistry, genomics and ultra high-throughput screening. The Company currently has research collaborations with Janssen Pharmaceutica, N. V. to discover oncology therapeutics and diagnostics based on cell cycle regulation and with Pfizer Inc. to discover human and veterinary drugs for asthma and allergy based on IgE regulation in B cells. Rigel also has research programs exploring the regulation of mast cell activation in allergy/asthma and the elimination of early drug resistance in tumor cells.