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Program Overview
Ion channels are pipes in cell membranes that provide for and regulate the flow
of ions – positively or negatively charged molecules – in and out of cells.
They are critical for the essential functioning of many cell types.
As one example, ion channels play a critical role in the ability of electrically
excitable cells, such as neurons or muscle cells, to discharge. Drugs that
modulate ion channels on excitable cells have proven to be a very successful
therapeutic category, with dozens of such drugs on the market and commonly
prescribed for the treatment of various neurological and cardiovascular
disorders.
Synta has exclusive ownership of a portfolio of intellectual property and
promising drug candidates targeting novel ion channels on non-excitable cells,
such as cells from the immune system. Ion channels on non-excitable cells can
play an important role in certain cell signaling pathways. Because these
channels are often very specific to certain tissue or cell types, and their
role is critical to the functioning of those cells or tissues, ion channel
modulators offer the potential for highly targeted action to improve a disease
state.
Synta’s ion channel modulators block calcium entry into immune cells. By doing
so, these drug candidates inhibit cytokine release, T cell activation, and
immune cell proliferation. These compounds form the basis for a new class of
drug candidates for treating asthma, transplant rejection, allergies, cancer,
and other conditions.
See additional reference on ion channels.
CRAC Channel
Our lead compound series includes a highly potent inhibitor of the critical
channel in immune cell signaling known as the CRAC (Calcium Release - Activated
Calcium) channel, and has shown potent anti-inflammatory activity in
preclinical models. CRAC channels are critical to the activation of
T-lymphocytes, mast cells and other hematopoietic cells, as they provide the
primary route for calcium entry, which drives multiple cell signaling
processes. CRAC inhibitors would be a promising new drug category for the
treatment of several diseases including graft-versus-host disease (GVHD),
immune disorders, allergies, and asthma. The Synta compounds, which have
demonstrated highly potent inhibition of cytokine production (including IL-2
and TNFa), appear to offer the most potent and
selective CRAC inhibition seen to date.
Preclinical Data
Our CRAC inhibitors have shown potent anti-inflammatory activity in preclinical
models. Data have demonstrated that inhibition of both IL-2 and TNFa
with our CRAC inhibitor is comparable to or better than cyclosporin, a commonly
used medication designed to suppress the immune system.
Development Status
Animal studies are ongoing to optimize the safety, pharmacokinetics, and
efficacy of these molecules in disease models.
References for Ion Channels
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Current Drug Discovery, April 2004, 31 - 33: ‘Ion
channel drug discovery expands into new disease areas.’ Michael Xie,
Mats H Holmqvist and Albert Y Hsia.
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Cell, 2003, 115: 863 - 877: A key Role for TRPM7 Channels in Anoxic
Neuronal Death.
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Cell Calcium, 2003, 33: 311-321: CRAC Channels: activation, permeation,
and the search for a molecular identity.
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Cell, 2002, 108: 595 - 598: The TRP Channels, a Remarkable Functional
Family.
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