Compounds enter or leave the cell primarily through membrane transport proteins, such as ion channel proteins and ATP-driven pumps (ATPases). Membrane transporter proteins therefore play critical roles in a variety of cellular functions, such as intracellular homeostasis, signal transduction, cell metabolism, energy transduction and recognition processes in the immune system. Voltage-gated ion channels (VGICs) are transmembrane proteins that enable to mediate ion (Ca2+, Na+, K+) in response to membrane depolarization, thereby triggering a variety of cellular activities. Ion channels are most widely distributed in the tissues of living organisms and play an important role in numerous cell types as a large family of related genes with cell-specific expression patterns. This type of therapeutic target is most important in the development of new efficient medical therapies. Ion channels are therefore essential molecular targets in drug development and their modulators are a highly successful class of drugs.
BOC Sciences has designed its proprietary library containing structurally diverse screening compounds for the discovery of novel ion channel ligands.
Application of Ion Channels
Ion channels are well recognized as important therapeutic targets for the following diseases of:
- The central nervous system (CNS), e.g. sleep disorders, anxiety, epilepsy, pain
- The peripheral nervous system, e.g. anticonvulsant, analgesic, anti-inflammatory
- The cardiovascular system, e.g. ischemia, hypoxic conditions, stroke
Figure 1. Structure of the nicotinic acetylcholine receptors. (Karlin. 2002)
Ion Channel Focused Library Design
At BOC Sciences, in order to obtain molecules focused on ion channel targets, we apply both ligand-based and receptor-based approaches in the library design. We also provide KQCN2 (Kv7.2) Ion Channel Targeted Library, N-methyl-D-aspartate (NMDA) Receptor Screening Library, Calcium Ion Channel Library, Sodium Ion Channel Libraryand Ligand-Gated Ion Channel Library.
- Our library is capable of generating a wide range of lead-like compounds built on novel scaffolds with saturated rings that have been recognized as potential ion channel blockers
- Our experts can perform a pharmacophore ligand-based analysis on a reference set of over 1,000 highly active ligands (≤10 nM), generating ligands in which three major pharmacophore motifs occur
- BOC Sciences supports various optimized model for searching the lead-like portion of the BOC Sciences screening collection
- One of the common features of the derived pharmacophore is the presence of tertiary/secondary amino groups
- Additional compounds are added to the library after analysis of the privileged motifs of known ion channel blockers
Table1. Physicochemical parameters for the BOC Sciences Ion Channel Focused Library
| Parameter | Value |
| MW | 200-400 |
| LogP | -2-4 |
| Number of H Acceptors | 1-9 |
| Compounds with ‘undesirable’ functionalities | Removed |
| FSp3 | 0.1-1 |
| TPSA | 40-120 |
Ion Channel Focused Library Characteristics
- Our library is developed based on lead-compound oriented synthesis, with a focus on increasing novelty and structural diversity
- Favorable physicochemical parameters and solubility requirements
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Bioactivity and safety confirmed by preclinical studies and clinical trials
- Structural diversity, medicinal activity, and cellular penetration
- Structural document, IC50, and other chemical and biological data are provided
- All compounds are continually updated
- Compound cherry-picking service is provided
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of Ion Channel Focused Library design at competitive prices for global customers. Personalized and customized services of Ion Channel Focused Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Karlin. Ion channel structure: Emerging structure of the Nicotinic Acetylcholine receptors. Nature Reviews Neuroscience. 2002. 3: 102-114.
