Compounds for enzyme inhibition

US8324174B2 · kind B2 · utility

Assignee

• Onyx Therapeutics, Inc. · US

Inventors

• Mark S. Smyth · Foster City, US
• Guy J. Laidig · Menlo Park, US
• Ronald T. Borchardt · Lawrence, US
• Barry A. Bunin · San Mateo, US
• Craig M. Crews · New Haven, US
• John H. Musser · Alameda, US

Key dates

• Filing date: Dec 22, 2011
• Grant date: Dec 4, 2012
• Expiry date: Dec 22, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K5/0827
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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 at least three peptide units, 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.