Posted on Mar 6, 2006 in Cancer Research, Europe, Press Releases
BARCELONA, Spain | March 6, 2006 | The Business Intelligence firm La Merie S.L. reported today that antibodies are at the forefront of novel cancer therapeutics targeting the insulin-like growth factor-1 receptor (IGF-1R). Pfizer is leading the field with the fully human IgG2 antibody CP-751,871 under investigation for multiple myeloma and advanced non-small cell lung cancer. Five other companies are closely following with antibody projects. Only six companies are currently visible with small molecule inhibitors targeting the IGF-1R tyrosine kinase which are not always selective for IGF-1R. INSM-18 from Insmed and the University of California San Francisco is a dual inhibitor of IGF-1R and Her2/neu and is the only clinical stage IGF-1R small molecule antagonist (phase I/II in prostate cancer). These results and more were found in a search conducted by La Merie Business Intelligence published in the March 6 issue of R&D Pipeline News, edited by La Merie. The competitor analysis of CB1 antagonists can be acquired at www.pipelinereview.com, La Merieâ€™s News Center and Online Store.
Although the IGF-1 receptor was first cloned in 1986, it was the success of targeted drugs such as trastuzumab and imatinib that tyrosine kinase inhibitors and growth factor receptor blockers became hot targets. Now companies are aggressively pursuing compounds that target IGF-1R. Other reasons for the long delay in bringing compounds against IGF-1R into the clinic may be: 1) the fear that blocking Igf-1R in cancer therapy would also block the insulin receptor and signaling (70 % homology with IGF-1R) and, thus might be diabetogenic; and 2) the expression of IGF-1R in normal tissue throughout the body. Aventis selected an antibody which does not bind to the closely related insulin receptor. However, preclinical data indicate a limited spectrum of tumor cell lines against which the antibody was effective.
While antibodies are exquisitely selective inhibitors of the IGF-1R function by inducing rapid internalization and down regulation of the receptor, small molecule tyrosine kinase inhibitors suffer from a lack of selectivity because of binding to a well conserved site.
Immunoglobulins or antibodies are proteins that are shaped like a Y. These are produced by the immune system of the body and it stops the intruders from causing harm to the body. When the intruder gets into the body then this causes the immune system to get into action. The invaders are known as antigens and they can be a bacteria, virus or any other chemical.
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In fact, several of the IGF-1R tyrosine kinase inhibitors in development are dual inhibitors, and in general do not lead to internalization and downregulation. Nevertheless, small molecule IGF-1R inhibitors offer the advantage of the ability to control the duration of drug exposure in contrast to long-acting antibodies.
Apart from antibodies and small molecules, there are individual approaches using peptides, proteins or antisense oligonucleotides to antagonize IGF-1R. The latter one has been evaluated as a topical cream to treat patients with psoriasis, but needs further dose optimization.
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R&D Pipeline News is a premier information source about research and development projects in the pipeline of the biopharmaceutical industry. The periodical is directed to all stakeholders in R&D. The weekly publication comes in a rapid- and easy-to-screen tabular format and provides access to the original information source via hyperlinks. R&D Pipeline News covers all relevant treatment modalities and is directly delivered to the desktop via e-mail. More information about the journal, a free trial and subscriptions are available via La Merieâ€™s Business Intelligence Center www.pipelinereview.com.
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SOURCE: La Merie Business Intelligence