Voltage-gated calcium channels are responsible for a large diversity of physiological functions, which reflects the critical cellular role of calcium ions in linking electrical and biochemical signaling, as well as the ubiquitous role of intracellular calcium ions in the second-messenger pathway. Calcium ions that enter the cell through voltage-gated channels act as the second-messengers of electrical signaling, triggering many different cellular events. The development of improved or novel therapies based on targeting calcium ion channels presents both opportunities and challenges. Calcium ion channels are difficult for the discovery of target-based drugs, but are undoubtedly a key point of impact on human physiology and pathophysiology. Many marketed drugs, including nifedipine, nimodipine, ethosuximide, pregabalin, and ziconotide, exert therapeutic effects by inhibiting calcium channels.
BOC Sciences has designed a novel calcium ion channel library based on the knowledge of voltage-gated targeted library construction.
Figure 1. Structure and molecular assembly of voltage-gated calcium channels. (Bourinet, E.; et al. 2014)
Calcium Ion Channel Library Design
CD BioScience’ calcium ion channel library is built based on known chemotypes and molecules based on novel scaffolds identified in our in silico studies. Our team has performed a comprehensive analysis of known calcium channel blockers and carefully selected more than 6,000 of the most promising drug-like structures from the CD BioScience HTS compound collections.
- Privileged chemotypes
Dihydropyridines, GABA analogs, succinimides, 4-substituted prolamines and quinazolines
- Pharmacophore modeling
A variety of relevant calcium channel blockers are studied and tested for the pharmacophore modeling, resulting in approximately 1,700 compound set
- Scaffold jumping
Considering that structures of many known calcium channel blockers contain piperazine or 4-aminopiperidine, we use diamine core to replace these motifs which can significantly expand the diversity of compounds based on unique analogs of piperazine and 4-aminopiperidine
Table1. Physicochemical parameters for the BOC Sciences Calcium Ion Channel Library
| Parameter | Value |
| Number of Rotatable Bonds | 0-10 |
| Number of H Donors | 0-4 |
| Number of H Acceptors | 1-8 |
| Compounds with ‘undesirable’ functionalities | Removed |
| Number of Rings | 0-5 |
| Number of Aromatic Rings | 0-175 |
| Fsp3 | 0.38 |
| PSA | 140 |
| Lead-likeness | 86% |
Calcium Ion Channel Library Characteristics
- 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 Calcium Ion Channel Library design at competitive prices for global customers. Personalized and customized services of Calcium Ion Channel 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
- Bourinet, E.; et al. Calcium-permeable ion channels in pain signaling. Physiological Reviews. 2014. 94(1): 81-140.
