press release archive

Discovery of Peptides with Anti-Proliferative Effects

Publications Describe Technology with Broad Application for Drug Discovery in Various Therapeutic Areas

South San Francisco, CA - October 20, 2003

Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that it has discovered peptides with anti-proliferative activity from a functional screen using retroviral-delivered random peptide libraries. The results appeared in two related scientific papers co-authored by Rigel researchers published in the October issue of the peer-reviewed journal, Chemistry & Biology. The peptides discovered are novel and exhibited dose-dependent anti-proliferative effects on tumor cells while showing no signs of cytotoxicity – precisely the peptide characteristics the screen was designed to discover.

Broad Applicability
Rigel believes that its technology as described in these publications is broadly applicable to many diseases. The ability to discover peptides that alter or improve disease processes, such as proliferation in cancer, can facilitate the development of novel therapeutics. Most diseases can be modeled using functional assays with relevant read-outs, such as proliferation. Large, diverse peptide libraries can be screened in these assays in a high-throughput manner. Those peptides that are found to alter the disease process, such as preventing proliferation, may have therapeutic utility either as a peptide drug itself or as a starting point for small molecule drug discovery. In addition to cancer, Rigel has used this technology to initiate drug discovery in inflammatory diseases such as allergy and asthma and is currently applying it to Hepatitis C.

“The creation of diverse peptide libraries and subsequent analysis of their effects is a powerful tool for manipulating disease processes in a cellular context and for the discovery of drugs,” said Dr. Donald G. Payan, Chief Scientific Officer and Executive Vice President of Rigel. “This technology has proven valuable in numerous therapeutic research applications.”

Technology Coalescence
These papers outline the coalescence of a large number of key technologies, which allow this type of screening to occur. These technologies include large random diverse peptide library generation, retroviral technology to deliver these peptides into the cell, reporter proteins to identify markers of interest, inducible expression systems to regulate the intracellular expression of these peptides, high throughput FACS analysis, mass spec to identify interacting proteins and the creation of functional assays to model diseases. Rigel has been a pioneer in the creation of intracellular small cyclic peptide libraries, which are more stable than linear peptides and, as a result, offer a better opportunity for drug discovery (see Journal of Biological Chemistry, Vol. 227, No. 40, Kinsella, et al.). Rigel has industrialized these technologies, incorporating them into a cohesive and functional system, which, as these publications illustrate, may have an important role in the discovery of novel therapeutics.

Full text of the papers can be obtained at:
http://www.chembiol.com/

Cellular Localization and Antiproliferative Effect of Peptides Discovered from a Functional Screen of a Retrovirally Delivered Peptide Library
Yasumichi Hitoshi, Tarikere Gururaja, Denise M. Pearsall, Wayne Lang, Poonam Sharma, Betty Huang, Susan M. Catalano, John McLaughlin, Erlina Pali, Beau Peele, Jorge Vialard, Michel Janicot, Walter Wouters, Walter Luyten, Mark K. Bennett, Dave C. Anderson, Donald G. Payan, James B. Lorens, Jacob Bogenberger and Susan Demo.

Cellular Interacting Proteins of Functional Screen-derived Antiproliferative and Cytototoxic Peptides Discovered using Mass Spectrometry Based Shotgun Peptide Sequencing
Tarikere Gururaja, Weiquin Li, Susan Catalano, Jacob Bogenberger, Jing Zheng, Bernd Keller, Jorge Vialard, Michel Janicot, Liang Li, Yashumichi Hitoshi, Donald G. Payan and D. C. Anderson.

About Rigel (www.rigel.com)
Rigel’s mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. Rigel has identified three lead product development programs: mast cell inhibition to treat immunologic diseases such as asthma/allergy and autoimmune disorders, antiviral agents to treat hepatitis C, and ligases a new class of cancer drug targets. Rigel has begun clinical testing of its first product candidate, R112, for allergic rhinitis, and it plans to begin clinical trials of three additional drug candidates, for the treatment of hepatitis C, rheumatoid arthritis and asthma by the end of 2004.

This press release contains “forward-looking” statements, including statements related to the applicability of Rigel’s technology and the timing and subject matter of future clinical trials. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “plans,” “believes” and similar expressions are intended to identify these forward-looking statements. There are a number of important factors that could cause Rigel’s results to differ materially from those indicated by these forward-looking statements, including risks associated with the development of its technology, the timing and success of clinical trials and the commercialization of product candidates, as well as other risks, detailed from time to time in Rigel’s SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2003 and Annual Report on Form 10-K, as amended, for the year ended December 31, 2002. Rigel does not undertake any obligation to update forward-looking statements.