DIARYL UREA COMPOUNDS AS ANTICANCER AGENTS VIA INHIBITION OF THE IGF-IR

BACKGROUND:

Receptor tyrosine kinases (RKTs) are transmembrane proteins that typically contain an extracellular ligand binding domain and an intracellular tyrosine kinase domain. In most cases, the receptor is relatively inactive until stimulated by its ligand. After activation, the RTKs undergo autophosphorylation and then, via their substrate tyrosine kinase activity, phosphorylate and activate intracellular signalizing systems, leading to increased mitogenesis and decreased apoptosis. One such RTK, the insulin-like growth factor receptor (IGF-IR) is a particularly attractive target for therapeutic interventions against abnormal growth. The IGF-1R has been shown to play a role in three key aspects of cancer development and proliferation: malignant transformation, stimulation of cancer cell growth, and protection against apoptosis.

DESCRIPTION:

UCSF researchers have discovered that a class of compounds, diaryl ureas, are effective antagonists of IGF-1R. The lead diaryl urea compound directly and selectively inhibits IGF-1R in isolated receptor preparations and cultured breast cancer cells. In addition, diaryl urea treatment was found to reduce breast cancer cell growth in cell culture and tumor growth in vivo. As such, diaryl urea compounds have the potential to become effective small molecule inhibitors for the treatment of essentially any cancer in which the IGF-1R plays an active role and where suppressing the activity of IGF-1R ameliorates the disease condition.

PATENT STATUS: U.S. Patent No. 6,337,338 issued January 8, 2002 and assigned to The Regents of the University of California

REFERENCE: Mol Cancer Ther. 2006 Apr;5(4):1079-86.

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

Ha Nguyen, Ph.D.
Licensing Associate
(415) 353-4661 phone
(415) 348-1579 fax
ngoc-ha.nguyen@ucsf.edu

Reference: OTM Case #SF2003-017