Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

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

To: tuck who wrote (2425)	6/28/2005 4:57:57 PM
From: tuck	Respond to of 3044

CXCR3 is not targeted by compounds in the Millenium pipeline, i.e., this appears to be a new approach for them. Presumably I-TAC (4-73) is the compound they are starting with, but the patent application mentions antibodies. More from the same team: >>J. Biol. Chem., Vol. 278, Issue 1, 289-295, January 3, 2003 Structure-Function Relationship between the Human Chemokine Receptor CXCR3 and Its Ligands* Ian Clark-Lewis§, Ivan Mattioli¶, Jiang-Hong Gong, and Pius Loetscher¶§ From the Biomedical Research Centre and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada and the ¶ Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland Received for publication, September 16, 2002, and in revised form, October 30, 2002 I-TAC, IP10, and Mig are interferon- inducible CXC chemokines that share the same G-protein-coupled receptor CXCR3, which is preferentially expressed on Th1 lymphocytes. We have explored the structure-function relationship of the CXCR3 ligands, in particular of I-TAC, which has highest affinity for CXCR3 and is the most potent agonist. A potent antagonist for CXCR3 was obtained by NH2-terminal truncation of I-TAC. I-TAC (4-73), which lacks the first three residues, has no agonistic activity but competes for the binding of I-TAC to CXCR3-bearing cells and inhibits migration and Ca2+ changes in such cells in response to stimulation with I-TAC, IP10, and Mig. It does also not induce internalization of CXCR3, which is in support of the lack of agonistic effects. Hybrid chemokines between I-TAC and IP10 were used to identify regions responsible for the higher activity of I-TAC. I-TAC-like IP10 analogs are obtained by substituting the NH2 terminus (residues 1-8) or N-loop region (residues 12-17) of IP10 with those of I-TAC, suggesting that the differences in function of the CXCR3 ligands can be assigned to distinct regions and that these regions are interchangeable. Structure-activity studies with Mig showed that the extended basic COOH-terminal region, which is not present in I-TAC and IP10, is important for binding and activity.<< jbc.org Also a freebie. Cheers, Tuck