SOUTH SAN FRANCISCO, Calif., Nov. 3 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc. today announced two publications in the October 24 issue of Methods in Enzymology (Volume 399) relating to its ubiquitin ligase program. Ubiquitin ligases are enzymes that regulate protein degradation within the cell, affecting many important cellular functions, including cell division. Targeting ligases represents a novel approach to treating diseases where normal cellular processes are out of balance.
“Ubiquitin ligases are important targets for the discovery of potential treatments for oncology, inflammatory and viral diseases,” said Donald G. Payan, M.D., executive vice president and chief scientific officer of Rigel. “Since they are numerous and modular, these ligases provide the opportunity to intervene with a disease in a highly specific fashion, potentially improving efficacy and minimizing side-effects.”
The first publication highlights a Fluorescence Resonance Energy Transfer (FRET)-based assay that can monitor the kinetics of enzymatic activity across a wide range of ligases to give more detail about how the compounds work. The second article details a high throughput screening process that Rigel has developed to screen the anaphase-promoting complex (APC), an E3 ubiquitin ligase under scrutiny as an anti-cancer target. APC leads to degradation of key cell cycle proteins and is responsible for completing the final steps of mitosis. Therefore, APC inhibition may modulate cell proliferation and could have anti-tumor effects.
Rigel has been issued patents covering both of these ligase screening methodologies, and expects to receive additional patents in the area of ligase technology within the next year.
A Homogenous FRET Assay System for Multi-ubiquitin Chain Assembly and Disassembly
Ubiquitin modification of target proteins has been implicated in a wide array of cellular processes including cell biogenesis. In order to better understand how Ubiquitin contributes to protein degradation and modification, Rigel scientists developed a homogenous, FRET-based assay that can monitor every reaction step involved in ubiquitin attachment to, or detachment from, substrate protein molecules.
The homogenous nature of the FRET assay was found to offer significant advantages over conventional methods. This assay allowed researchers to monitor both ubiquitin polymerization and depolymerization reactions in the same reaction mixture. In general, the homogenous FRET assay was found to have the potential to improve the throughput and reliability of screening for new drug leads in cancer biology.
High-throughput Screening (HTS) for Inhibitors of the E3 Ubiquitin Ligase APC
In the study, researchers at Rigel established a plate-based in vitro ubiquitination assay that screens for small molecule inhibitors of APC E3 ligase activity. The screen successfully identified novel small molecule compounds that potently inhibit APC ligase activity.
Rigel: A Leader in Ubiquitin Ligase Discovery
Rigel is a leader in investigating and characterizing the ubiquitin ligase system for the discovery and development of potential new therapeutics. The company has initiated one of the industry’s broadest efforts, working on the development of numerous ligase targets. Rigel was one of the first companies to discover potent and highly selective small molecule inhibitors of ubiquitin ligases. Some of these inhibitors have shown positive activity in animal models of disease. Rigel has been collaborating with Daiichi Pharmaceuticals Co., Ltd., since 2002 to identify specific small molecule drug candidates against a ligase target that controls cancer cell proliferation through protein degradation. Recently, Daiichi selected two potent and selective small molecule compounds to advance into preclinical development. In addition, Rigel entered into a broad collaboration agreement in November 2004 with Merck & Co., Inc. to investigate ubiquitin ligases to find treatments for cancer and potentially other diseases.
About Rigel
Rigel is a late-stage drug development company that discovers and develops novel, small-molecule drugs for the treatment of inflammatory diseases, cancer and viral diseases. Our goal is to move one new product candidate for a significant indication into the clinic each year. We have achieved this goal since 2002. Our pioneering research focuses on intracellular signaling pathways and related targets that are critical to disease mechanisms. Rigel’s productivity has resulted in strategic collaborations with large pharmaceutical partners to develop and market our product candidates. We have product development programs in allergy/asthma, rheumatoid arthritis and cancer.
This press release contains “forward-looking” statements, including statements related to Rigel’s plans to pursue clinical development of product candidates and the timing thereof and the potential efficacy of product candidates. 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,” “intends,” “expects” 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 timing and success of pre-clinical studies and clinical trials, 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, 2005. Rigel does not undertake any obligation to update forward- looking statements.
Contact: Raul Rodriguez Phone: 650-624-1302 Email: invrel@rigel.com Media Contact: Carolyn Bumgardner Wang, WeissComm Partners, Inc. Phone: 415-946-1065 Email: carolyn@weisscommpartners.com
Photo: http://www.newscom.com/cgi-bin/prnh/20030226/RIGLLOGOAP Archive: http://photoarchive.ap.orgPRN Photo Desk photodesk@prnewswire.comRigel Pharmaceuticals, Inc.
CONTACT: Raul Rodriguez of Rigel Pharmaceuticals, Inc., +1-650-624-1302,or invrel@rigel.com; or media, Carolyn Bumgardner Wang of WeissCommPartners, Inc., +1-415-946-1065, or carolyn@weisscommpartners.com, forRigel Pharmaceuticals, Inc.
Web site: http://www.rigel.com/
