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

To: mopgcw who wrote (304)	10/30/2007 9:56:22 AM
From: tuck	Read Replies (1) \| Respond to of 566

[A Class of Small Molecules that Inhibit TNFalpha-Induced Survival and Death Pathways via Prevention of Interactions between TNFalphaRI, TRADD, and RIP1] >>Chem Biol. 2007 Oct;14(10):1105-18. A Class of Small Molecules that Inhibit TNFalpha-Induced Survival and Death Pathways via Prevention of Interactions between TNFalphaRI, TRADD, and RIP1. Gururaja TL, Yung S, Ding R, Huang J, Zhou X, McLaughlin J, Daniel-Issakani S, Singh R, Cooper RD, Payan DG, Masuda ES, Kinoshita T. Rigel Pharmaceuticals, Incorporated, 1180 Veterans Boulevard, South San Francisco, CA 94080, USA. Small-molecule library screening to find compounds that inhibit TNFalpha-induced, but not interleukin 1beta (IL-1beta)-induced, intercellular adhesion molecule 1 (ICAM-1) expression in lung epithelial cells identified a class of triazoloquinoxalines. These compounds not only inhibited the TNFalpha-induced nuclear factor kappaB (NFkappaB) survival pathway but also blocked death-pathway activation. Such dual activity makes them unique against other known NFkappaB-pathway inhibitors that inhibit only a subset of TNFalpha signals leading to increased TNFalpha-induced cytotoxicity. Interestingly, these compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation. Further study showed that they blocked ligand-dependent internalization of the TNFalpha-TNFalphaR complex, thereby inhibiting most of the TNFalpha-induced cellular responses. Thus, compounds with a triazoloquinoxaline scaffold could be a valuable tool to investigate small molecule-based anti-TNFalpha therapies.<< Parking. Don't know if relevant to Rigel drug discovery, i.e. is there a lead compound in there? Cheers, Tuck