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|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|
|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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