Rigel Ligase Research Featured at AACR Symposium
Updated: Friday, November 1, 2002 05:44 PM ET Printer-friendly version
Enzymes That Regulate Cell Division Believed to Hold Promise for New Cancer Therapies
SOUTH SAN FRANCISCO, Calif., Nov. 1 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc., (Nasdaq: RIGL, news) presented an update of the company's research program in ubiquitin ligases at a special symposium being held this week by the American Association of Cancer Research (AACR). Ligases, a class of enzyme that regulates cell proliferation, have recently become the subject of intense interest among oncology researchers as a potential new strategy for treating cancer.
"We're pleased to be one of only a small number of companies invited to participate in this highly academic forum," said Donald G. Payan, M.D., Rigel's executive vice president and chief scientific officer. "We believe this reinforces Rigel's leadership in the ligase arena."
Rigel's research focuses on identifying a broad number of ligases and then linking these with their specific function or disease state, so as to home in on those that would make good drug targets. The company has amassed a significant body of knowledge about ligases as a class, and already has a series of potential ligase inhibitors that block proliferation of several types of tumor cell in culture. Rigel is now working to identify the most promising of these drug candidates to move into clinical evaluation.
Growing Scientific Attention
Ligases are part of a system within human cells, called the ubiquitin-proteasome pathway that mediates the degradation of proteins. Breakdown of proteins, in turn, affects many important cellular functions, including cell division. Because unchecked cell division is the hallmark of cancer, researchers believe that this part of the cell machinery represents a compelling target for cancer therapies.
The fact that major cancer research organizations are convening ligase symposia -- in addition to AACR, the National Cancer Institute will hold its own meeting later this year-points to the level of scientific attention now being paid to ligases. In fact, within the scientific community, the value of these enzymes as drug targets has been compared to that envisioned for kinases in the 1990s. Kinases are a class of compound that has now assumed major importance in pharmaceutical research, spurred in part by the success of drugs like Novartis's Gleevec(TM).
"There's no doubt that ligases and other components of the ubiquitin-proteasome pathway are becoming an important target in oncology drug development," said Raymond Deshaies, Ph.D., associate professor at the Howard Hughes Medical Institute/California Institute of Technology and co-chairman of the symposium. "The amount of scientific inquiry in this field has grown significantly in just the past few years, and it is becoming more and more obvious that the ubiquitin-proteasome pathway plays a key role in cancer. It's certainly possible that the enzymes of the ubiquitin proteasome pathway -- including ligases, isopeptidases and the proteasome itself -- could represent one of the next major breakthroughs in cancer treatment, much as kinases did five years ago."
Technology Innovation to Help Address Difficult Targets
Complex enzymatic systems such as ligases have historically been very difficult to address in the pharmaceutical R&D process. To tackle this problem, Rigel has developed a new technologic innovation that significantly improves the ability to influence the intricate protein interactions that direct cell function and thus uncover possible new targets for drug intervention.
Rigel's new approach uses small ringed molecules, called cyclic peptides that can bind to sites not readily accessible through other techniques. Rigel then uses its core technology to introduce millions of these molecules into a particular type of cell to see if the function of the cell can be changed in the desired way, thereby suggesting a potential treatment approach. In addition to uncovering novel targets, this new research technique can directly produce drug leads, as cyclic peptides themselves can be used as drugs. Rigel reported on this first-of-its-kind cyclic peptide technology in mammalian cells in the October issue of Journal of Biological Chemistry.
"We believe this is a true leap forward in functional genomics target discovery and, in some cases, can even give us a headstart in creating drug molecules to address these intracellular targets," Dr. Payan noted. "This technology also highlights Rigel's success in developing new and better tools to continually improve the efficiency and strength of our drug discovery efforts."
About Rigel
Rigel's mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. The company's business model is to develop a portfolio of drug candidates and to take these through phase II clinical trials, after which Rigel intends to seek commercialization partners for completion of clinical evaluation, regulatory approval and marketing. Rigel has identified three areas for its lead product research programs: mast cell activation to treat immunologic diseases such as asthma/allergy and autoimmune disorders; an antiviral agent to treat hepatitis C; and ubiquitin ligases, a new class of cancer drug target. Rigel has begun clinical testing of its first product, for allergic rhinitis, and plans to follow this with two additional drugs in the clinic by the end of 2003. Rigel's approach to drug discovery is based on advanced, proprietary functional genomics techniques that allow the company to identify targets with a demonstrable role in a disease pathway and to efficiently screen for those that are likely to be amenable to drug modulation. |
