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Antibodies are the first wave
of IGF-1R antagonists for cancer therapy
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 Merie’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. 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.
About R&D Pipeline News
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 Merie’s Business Intelligence Center
www.pipelinereview.com .
About La Merie
La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide
high quality R&D information to the biopharmaceutical industry. La Merie offers
individual consultancy services and publishes reports and periodicals.
They publish two weekly
newsletters - apply for a FREE three week trial:
R&D Pipeline News is a premier
information source about research and development projects in the pipeline of
the biopharmaceutical industry and 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.
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