Onyx Therapeutics, Inc.

Cv Therapeutics, Inc.

Other

Proteolix, Inc.

Kevin D Shenk

Guy J Laidig

Han-Jie Zhou

Jeff A Zablocki

Prabha N Ibrahim

Mark Stephen Smyth

Mark K Bennett

Francesco Parlati

Catherine Sylvain

Elfatih O Elzein

Congcong M Sun

Venkata Poornapragnacharyulu Palle

Robert H Jiang

Christopher F Morrison

Kenneth S Rehder

Thao Perry

Xiaofen Li

Dengming Xiao

John H Musser

Dmitry Koltun

Craig M Crews

Richard M Lawn

Michael G Campbell

Ronald T Borchardt

Barry A Bunin

Peggy A Radel

Elfaith O Elzein

William Shirley

Reina Natero

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. 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. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

Compounds for enzyme inhibition

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Compounds for immunoproteasome inhibition

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 chymotrypsinlike 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.

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Palo Alto, CA, United States of America

Kevin D Shenk