G protein-coupled receptor (GPCRs) are the largest family of cell surface receptors and are important drug targets. In recent years, a diversity of advanced biochemical and biophysical technologies have been used to study GPCRs. GPCRs have multiple modes of activation to promote the drug development, providing a theoretical basis for the development of GPCR-targeted functionally selective drugs. In classical GPCR activation, the GPCR couples to various heterotrimeric G proteins on the membrane and then activates downstream signaling pathways.
BOC Sciences has designed a novel GPCR screening library to target compounds for screening in GPCR-related drug discovery programs.
Figure 1. Scheme of GPCR internalization assays. (Haasen, D.; et al. 2006)
Receptor-based GPCR Targeted Library Design
We mainly employ the following computational methods, such as homology modeling, reference compound set selection and analysis, molecular dynamics, molecular docking and in silico version of high-throughput screening (HTS).
- Firstly, each GPCR target is prepared and optimized using Schrödinger's equation
- Then, a number of individual protein structures will be further relaxed using molecular dynamics simulations in GROMACS software
- The reference set of compounds selected for screening validation contained known and proven inhibitors of GPCRs derived from various database
- Glide docking and modeling protocols are available for the docking and screening procedures
- Ultimately, over 8,500 drug-like screening compounds that have predicted GPCR antagonist activity against 16 GPCR targets are selected
- Ranking of potential GPCR ligand hits is carried out based on scoring values obtained from reference set
Table1. The list of GPCR target proteins and the corresponding number of compounds obtained by means of HTS
| Adenosine receptor | A2A (197 compounds) |
| A2B* (1054 compounds) | |
| A3* (149 compounds) | |
| Chemokine receptor | CXCR4 (805 compounds) |
| CCR5* (367 compounds) | |
| Histamine receptor | H3* (149 compounds) |
| H4* (1,131 compounds) | |
| Opioid receptor | Delta-type (825 compounds) |
| Kappa-type (696 compounds) | |
| Mu-type (669 compounds) | |
| Dopamine D3 receptor (1,911 compounds) | |
| GABA receptor subunit (295 compounds) | |
| Muscarinic acethylcholine receptor type (21,126 compounds) | |
| Sphingosine 1-phosphate receptor (822 compounds) | |
| Serotonine receptors (type 5HT1B) (650 compounds) |
Receptor-based GPCR Targeted Library Characteristics
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Valuable tool for finding the most promising GPCR drugs
- 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 Receptor-based GPCR Targeted Library design at competitive prices for global customers. Personalized and customized services of Receptor-based GPCR Targeted 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
- Haasen, D.; et al. G protein-coupled receptor internalization assays in the high-content screening format. Methods in Enzymology. 2006. 414(5): 121-139.
