University of California

Kezar Life Sciences

Principia Biopharma Inc.

John William Taunton

Michael S Cohen

Shyam Krishnan

Jesse McFarland

David Michael Goldstein

Kevan M Shokat

Dustin L McMinn

Kenneth Albert Brameld

Wendell A Lim

Chia-Yung Wu

Chao Zhang

Phillip Patrick Sharp

Jonathan Choy

Rebecca Maglathlin

Iana Serafimova

Rand Miller

Ville Paavilainen

Jesse Mcfarland

Provided herein are compounds that inhibit protein secretion, e.g., via inhibition of Sec61. Also provided are compositions of the inhibitor compounds, and methods of using these inhibitors. The compounds disclosed herein can be used, e.g., for the treatment of cancer, arthritis, and/or inflammation.

CDP protein secretion inhibitors

The present disclosure provides conditionally active, heterodimeric polypeptides. The conditionally active, heterodimeric polypeptides are active in the presence of a dimerizing agent that induces dimerization of the polypeptides of the heterodimer. A conditionally active, heterodimeric polypeptide of the present disclosure is useful in a variety of research and treatment methods, which are also provided.

Conditionally active heterodimeric polypeptides and methods of use thereof

Provided herein are compounds such as the compounds having the structure of Formula (XI) and methods of using the same, such as methods of inhibiting kinases.

Kinase inhibitors

Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.

Inhibition of protein kinases having one or more cysteine residues within the ATP binding site is effected by contacting the kinase, per se or in a cell or subject, with an inhibitory-effective amount of a compound having a heterocyclic core structure comprised of two or more fused rings containing at least one nitrogen ring atom, and an electrophilic substituent that is capable of reacting with a cysteine residue within the ATP binding site of a kinase. Preferred compounds include certain pyrrolopyrimidines and oxindoles having such an electrophilic substituent and optionally an aromatic or heteroaromatic substituent that is capable of interacting with a threonine or smaller residue located in the gatekeeper position of the kinase. Kinases lacking such cysteine residues may be engineered or modified so that they are capable of being inhibited by such compounds by replacing a valine or other amino acid residue within the ATP binding site by a cysteine residue.

Selective serine/threonine kinase inhibitors

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San Francisco, CA, United States of America

John William Taunton