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Solid tumors

Insulin-like growth factor-1 receptor (IGF1R; CD221); insulin receptor substrate 1 (IRS1); IRS2

SAR, cell culture and mouse studies suggest compounds that cause degradation of IRS1 and IRS2 could be useful for treating cancer. SAR and cell culture studies identified allosteric inhibitors of IGF1R that caused hyperphosphorylation and degradation of IRS1 and IRS2. In mouse xenograft tumor models, the most effective of these compounds decreased tumor growth and increased survival compared with vehicle. In cell lines derived from BRAF inhibitor-resistant tumors, the compounds increased cancer cell death compared with no treatment. Next steps include long-term toxicology studies and other preclinical development work.
At least 18 products that target IGF1R or IRS1 are in preclinical through Phase III testing for various cancer indications (see IRS audit for tumors, page 1).

SciBX 6(20); doi:10.1038/scibx.2013.493
Published online May 23, 2013

Patent pending; available for licensing or partnering from NovoTyr Therapeutics Ltd.

Reuveni, H. et al. Cancer Res.; published online May 7, 2013;
Contact: Alexander Levitzki, The Hebrew University of Jerusalem, Jerusalem, Israel