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Details for Patent: 8,198,270

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Details for Patent: 8,198,270

Title:Compounds for proteasome enzyme inhibition
Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.
Inventor(s): Smyth; Mark S. (San Mateo, CA), Laidig; Guy J. (Menlo Park, CA)
Assignee: Onyx Therapeutics, Inc. (South San Francisco, CA)
Filing Date:Aug 08, 2005
Application Number:11/658,983
Claims:1. A method for treating bone loss, which comprises administering a therapeutically effective amount of a compound having the following formula: ##STR00024## pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the bone loss is associated with osteoporosis.

3. A method for treating graft-versus-host disease, which comprises administering a therapeutically effective amount of a compound having the formula: ##STR00025## pharmaceutically acceptable salt thereof.

4. A method for inhibiting antigen presentation in one or more cells, which comprises contacting at least one of the one or more cells with a compound having the following formula: ##STR00026## or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the contacting is in vitro.

6. The method of claim 4, wherein the contacting is in vivo.
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