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Ligand channels. Ligand-Gated Ion Channels Library

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ChemDiv’s library of small molecule agents targeting ligand-gated ion channels contains 4,000 compounds.

Ligand-gated ion channels (LGICs) are essential in mediating intercellular communication. They convert the binding of neurotransmitters, released from the presynaptic membrane, into an ion flux across the postsynaptic membrane. These channels are integral membrane proteins featuring an orthosteric binding site for the neurotransmitter and an ion channel that crosses the membrane. Being inactive, the channel remains closed. Following the binding of an agonist, the channel induces a conformational change that opens the gate, allowing either cations or anions to diffuse through the pore at rates of tens to hundreds of millions of ions per second. LGIC’s role in neurotransmission is well studied, however, recent findings have revealed their vital role in non-excitable cells, such as endothelial cells, suggesting a broader functional role for those receptors beyond the peripheral and central nervous systems. This expanded understanding of LGICs underscores their potential as promising targets for the development of novel therapeutic agents.

LGICs have been shown to play a critical role in the development of a vast array of diseases, particularly neurodegenerative disorders. They include Alzheimer's Disease and Parkinson's Disease, epilepsy, hyperekplexia, and neuropathic pain. All of them are caused by significant dysfunctions in LGIC.

LGIC inhibitors are valuable in developing novel therapies for neurological conditions such as epilepsy, anxiety, and neurodegenerative diseases (Alzheimer's and Parkinson's). They also have potential applications in pain management, specifically in conditions involving neuropathic pain, as normal ion channel function is impaired. LGIC inhibitors selectively target these channels and provide a means to restore normal cellular function, offering therapeutic benefits with potentially fewer side effects compared to broader-acting drugs. The specificity and diversity of LGICs make them attractive targets, allowing for the development of more targeted therapies that can address a wide range of pathological conditions.

Our library of LGIC inhibitors is a promising tool for drug discovery and it offers a diverse range of compounds that can be screened for potential therapeutic effects in various neurological and psychiatric disorders. This library accelerates the process of identifying and optimizing novel inhibitors via providing access to a wide array of LGIC-targeting molecules, and it streamlines the development of the novel effective therapies for conditions associated with LGIC dysfunction.

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