Novel Selective Inhibitors of p90 ribosomal S6 kinases: RSK1 and RSK2

BACKGROUND:  Protein kinases act at critical control points in many cellular processes, including cell growth and differentiation, making protein kinases a very attractive target for drug design and treatment of disorders such as cancer and inflammatory diseases. Previously, protein kinase ATP binding regions have been targeted for inhibition, resulting in the identification of multiple tight binding compounds.  However, although the ATP binding site is an attractive target due to its deep hydrophobic pocket, all of the over 500 protein kinases encoded by the human genome contain similar ATP binding sites.  This structural uniformity has made designing selective protein kinase inhibitors difficult, while nonselective inhibition of multiple protein kinases could lead to undesirable side-effects.  Therefore, selective kinase inhibitors represent potentially useful therapeutic agents.

TECHNOLOGY:   UCSF researchers have designed novel small molecules that target RSK1 and RSK2 protein kinases (1).  The Rsk serine/threonine protein kinases have critical functions in the Ras/MAP kinase signaling pathway, a pathway which is deregulated in many human cancers.  These novel inhibitors have already been shown to selectively kill multiple myeloma (MM) cell lines (2).  Additionally, recent animal studies have implicated RSK2 in cardiac ischemia-reperfusion injury as well as diabetic cardiomyopathy.

ADVANTAGES:  These novel RSK1 and RSK2 inhibitors:

• Show selectivity for the targeted kinases
• Are cell permeable
• Show inhibition of kinase activity in vitro and in cell-based assays

APPLICATIONS:

• Potential therapeutics for certain cancer types, such as multiple myeloma.
• Potential therapeutics for cardiac diseases.

STATUS OF IP:  US Patent Application No. 20070082884, and PCT Publication No. WO2007/038613

CASE NO:  SF2003-057

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Ellen S. Kats, Ph.D.
Licensing Associate
Phone: (415) 514-8210
Fax: (415) 348-1579
ellen.kats@ucsf.edu

Reference: OTM Case #SF2003-057