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Biotech / Medical : Rigel Pharmaceuticals, Inc. (RIGL) -- Ignore unavailable to you. Want to Upgrade?

To: mopgcw who wrote (148)	10/27/2003 9:35:12 AM
From: tuck	Respond to of 566

>>SOUTH SAN FRANCISCO, Calif., Oct. 27 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL - News) today announced that the results of a recent study demonstrating the potential of a new class of drug candidates, syk kinase inhibitors, to treat inflammatory diseases such as rheumatoid arthritis (RA), will be presented at a podium presentation of the American College of Rheumatology's Annual Scientific meeting. In the study, one of Rigel's first-generation compounds, R091, profoundly reduced clinical measures of arthritis and bone erosion in a key rat model of RA, demonstrating this class of drugs' potential use as therapy for autoimmune diseases such as RA. The results of the study will be presented by Ernest Brahn, M.D. at the American College of Rheumatology's annual ACR/ARHP Annual Scientific Meeting 2003 in Orlando, Florida on Tuesday, October 28, 2003. Dr. Brahn is Professor of Medicine and Rheumatology Program Director at the UCLA School of Medicine. "These findings represent one of the best results we have seen in this animal model," said Dr. Brahn, "Rigel's compounds may impart a new opportunity for treating this class of diseases." In a 28-day study with Rigel's R091 using syngeneic LOU rats, Dr. Brahn noted a dose-related reduction in the severity of bone destruction. This result was evident within the first 72 hours after arthritis onset and continued to improve throughout the study. The study consistently produced significant reductions in gauges of RA intensity at higher doses. Importantly, this was the case both with a prophylactic protocol, when the drug was given prior to the induction of disease, as well as in a treatment protocol, when the drug was given after the onset of disease. Dr. Brahn has determined that an inhibitor of syk kinase reduces severity of all aspects of collagen-induced arthritis, and this class of agents may have potential uses as therapies for autoimmune diseases such as RA. "Rigel's syk inhibitors appear to block release of all major downstream mediators of inflammation following the activation of the IgG receptor on inflammatory cells. This may have significant benefits in autoimmune diseases as the recent study by Dr. Brahn demonstrates," stated Donald Payan, M.D., Rigel's Chief Scientific Officer and Executive Vice President. Dr. Payan further stated, "R091 and its follow-up compounds may offer the potential to achieve better efficacy than current RA treatments by offering a more comprehensive approach by blocking all major inflammatory mediators but without the significant side effects of some of the current drugs. In addition, these compounds will be oral drugs offering improved delivery and patient compliance compared to the current injectable drugs." Rheumatoid arthritis is a chronic inflammatory disease affecting multiple tissues, but typically producing its most pronounced symptoms in the joints. It is often progressive and debilitating. The chronic inflammation of joints leads to the destruction of the soft tissue as well as to erosion of the articular surfaces of the bone. The disease is estimated to affect nearly one percent of the U.S. population, approximately 2.1 million people. (1) Currently, RA is not well treated with most therapies having significant potential side effects or other shortfalls. Today, RA patients receive multiple drugs dependent on the extent and aggressiveness of the disease. Patients with a mild-to-moderate form of the disease are offered a non- steroidal anti-inflammatory (NSAID) or a Cox-2 inhibitor. As the disease progresses, these drugs are then layered with more potent and potentially more toxic therapies. NSAIDs are supplemented with steroids and then a DMARD (disease-modifying anti-rheumatic drugs) such as methotrexate, an anti-cancer agent. Due to serious side effects, it is highly desirable to reduce patient reliance on both steroids and conventional DMARDs such as methotrexate. The other major class of RA drugs, are the TNF-blocking agents. These block only the inflammatory mediator TNF and are all delivered via injection. Rigel believes its syk kinase inhibitors have the potential to achieve better efficacy than current agents in RA by blocking all major inflammatory mediators, including TNF, various interleukins, and other mediators. As such, Rigel's agents may become the first-line DMARD with greater efficacy, safety and improved delivery and patient compliance. Rigel continues to work to discover compounds that target and prevent the secretion of inflammatory mediators by inhibiting syk kinase. R091 is not intended to move into the clinic since far more potent third and forth- generation compounds have been developed. Some of these compounds are at least two orders of magnitude more potent than R091 at syk kinase inhibition and with improved pharmaceutical properties. Rigel anticipates selecting a clinical candidate shortly from among its forth-generation syk kinase inhibitors and aims to file an IND in 2004.<< snip Cheers, Tuck

To: mopgcw who wrote (148)	10/30/2003 10:48:48 AM
From: tuck	Read Replies (1) \| Respond to of 566

>>Chem Biol. 2003 Oct;10(10):975-87. Cellular localization and antiproliferative effect of peptides discovered from a functional screen of a retrovirally delivered random Peptide library. Hitoshi Y, Gururaja T, Pearsall DM, Lang W, Sharma P, Huang B, Catalano SM, McLaughlin J, Pali E, Peelle B, Vialard J, Janicot M, Wouters W, Luyten W, Bennett MK, Anderson DC, Payan DG, Lorens JB, Bogenberger J, Demo S. Rigel Pharmaceuticals Inc., 94080, South San Francisco, CA, USA We have generated a random peptide library fused to GFP in a retroviral vector system and used this library to screen for peptides inhibiting tumor cell growth. Four unique peptide sequences were isolated that exhibited antiproliferative effects and that specifically localized to the plasma membrane and cytoplasmic granular compartments. Mutational analysis revealed critical residues in each peptide sequence and demonstrated a correlation between peptide subcellular localization and antiproliferative activity. Synthetic analogs of the peptides with poly-lysine internalization sequences, but not loss-of-function mutant peptides, competed for subcellular localization of the parent GFP-fused peptides. The synthetic peptides exhibited dose-dependent antiproliferative effects in tumor cells, while mutant peptides had no effect. Our screening approach using retrovirally expressed intracellular peptides enables identification of unique sequences with a specific biological function and with potential as therapeutics.<< Cheers, Tuck