PLATFORM TECHNOLOGIES
Icagen has established an integrated set of core technologies for the discovery of drugs that act upon ion channel targets. Our platform technologies, which we apply across all of our drug discovery programs, broadly cover the key disciplines of importance to ion channel drug discovery, including molecular biology, electrophysiology, high throughput screening, chemistry, bioanalytics and pharmacology.
Comprehensive Library of Ion Channel Genes
As the foundation of Icagen's ion channel focused drug discovery efforts, we have cloned over 300 human ion channel genes, which we believe represent substantially all of the human ion channel genome. We have an extensive collection of cell lines comprising these genes in a variety of specific configurations which mimic native channels in the human body and which can be used in screening assays.
This comprehensive library of clones, cell lines and assays enables us to rapidly initiate new ion channel drug discovery programs; perform high throughput screens in parallel across multiple ion channel targets; and understand the relationships among various ion channels and classes of compounds that are active against ion channels.
Parallel High Throughput Screening Systems
We conduct high throughput screening against our ion channel targets in a parallel manner. Specifically, as we screen a particular ion channel target with a library of small molecules, we simultaneously screen other important safety or selectivity ion channel targets with the same set of compounds. The data we derive from these parallel screens provide important information not just on the potency of the compounds on the target of interest, but also on the potential of these compounds to cause side effects from activity at other ion channels. This approach enables us to focus our medicinal chemistry efforts only on those compounds that demonstrate both potency and selectivity for the target, thereby eliminating compounds that are likely to induce significant side effects. We believe that we apply this type of parallel screening earlier in the drug development process than many other companies pursuing ion channels as targets and that this approach substantially increases our discovery efficiency.
Extensive Library of Ion Channel Focused Small Molecules
We have built a library of over 250,000 small molecules that have been selected for potential activity at ion channel targets. This library has been developed based upon our experience in working across a range of different ion channel targets. We have found that some families of compounds show increased levels of activity against particular classes of ion channels. Through our synthetic medicinal chemistry efforts, combined with our proprietary computational chemistry technology, we continually enrich our small molecule compound library with compounds that have demonstrated activity at ion channel targets.
Gene family library of 250,000+ small molecules clustered by
applicability to one or more channel types.
Chemistry Capabilities
Icagen's chemistry resources are focused on identifying compounds that potently and selectively modulate the targeted ion channel and that have drug-like characteristics. Our capabilities span the key disciplines of medicinal, combinatorial and computational chemistry.
We have developed a proprietary computational chemistry technology that we use to identify active compounds based upon the information provided by our high throughput screening systems. Through the application of statistical techniques, this computational chemistry technology uses the information on relevant chemical parameters of the active compounds to construct a mathematical model of the general properties of compounds that may be active against the targeted ion channel. We use this model to perform a computer search of our compound library, the libraries of our collaborators and commercially available libraries, as well as the millions of compounds accessible in silico, for compounds with potential activity against the target. Through this approach, we are able to generate an enriched library containing multiple classes of compounds with activity against the targeted ion channel for subsequent medicinal chemistry efforts. We refer to these compound libraries as Gene Family Libraries, or GFLs. These libraries are enriched for compounds that interact with specific ion channel families, resulting in higher compound hit rates with significantly less screening time and a markedly reduced need for large compound libraries, thereby accelerating our drug discovery process.
Extensive Database and Bioinformatics Platform
We have built an extensive database containing information on many ion channels across ion channel families. We use this database to capture information we have obtained from studying the interactions between ion channel targets and small molecule compounds, and we apply this information across our drug discovery programs. We have created a discovery informatics infrastructure that facilitates our efficient management of large and complex data sets representing valuable ion channel information. We organize this data in a format that is readily accessible by our scientists, thereby facilitating decisionmaking. Our database contains important information regarding the characterization of each of our targets and compounds; the potency and selectivity of particular compounds or groups of compounds against ion channel targets we have studied; bioanalytical and pharmacological data; and information accessed from other proprietary and publicly available databases and sources.
Electrophysiology Know-How and Technical Expertise
Electrophysiology is a critical component of ion channel drug discovery. Icagen has assembled an experienced electrophysiology group equipped with state-of-the-art technologies. The skill and expertise of our electrophysiology group enables us to understand the function of each of our ion channel targets under varying physiologic conditions and its modulation by drug candidates. Through the detailed analyses performed by this group, we are better able to understand the likely role of the channel in the tissue of interest and the likely effects of its modulation by small molecule compounds. In addition to our expertise in the application of traditional electrophysiologic techniques, we have also advanced our capabilities through the integration of recently developed high throughput electrophysiology equipment and techniques into our drug discovery process. Our capabilities include the ability to perform the following studies:
- Single cell patch clamp, current and voltage recordings in both cloned and native cells
- Oocyte expression studies and micro-electrode/whole-cell recordings in neuronal slice and cardiac preparations
- Medium and high throughput patch clamp recordings
Pharmacology and Bioanalytics Expertise
We conduct iterative in vitro and in vivo testing of our compounds to characterize their pharmacologic and pharmacokinetic properties in detail. We have on-site bioanalytic capabilities in order to rapidly provide our scientists with important data regarding compound pharmacokinetics and metabolism.
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