Currently, G protein-coupled receptors (GPCRs) are one of the most intensively studied drug targets, with more than 1/3 of approved drugs targeting GPCRs. They are substantial involved in human pathophysiology due to their pharmacological accessibility for small molecule drug discovery.
BOC Sciences can design a 2D similarity-based GPCR focused screening library based on known structure and activity data for some available GPCR-targeting compounds.
Figure 1. Regulation by internalisation of GPCRs. (Martins, S.; et al. 2012)
Library Design
- Firstly, a reference set of molecules with validated GPCR activity data is developed by applying a database with reliable sources
- Then, these compound molecules are narrowed down to meet high activity criteria, such as inhibition>50%, IC50, Ki, EC50 >1 μM, etc
- Next, a 2D fingerprint similarity search and Tanimoto index ≥0.85 are performed against the BOC Sciences HTS compound collection
- Finally, the resulting set of compounds is filtered using internal PAINS and toxicophore filters
The following are examples of the GPCR targets against:
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2D Similarity-based GPCR Focused Screening Library Characteristics
- At BOC Sciences, careful selection of GPCR-privileged scaffolds and common structural motifs with extension by 3D pharmacophore searches are supported to facilitate high-throughput screening for the discovery of novel GPCR ligands
- An additional subset of 2,200 small-molecule screening compounds is also provided based on known GPCR allosteric modulators
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Confirmed bioactivity and safety by preclinical studies and clinical trials
- Structural diversity, significant efficacy, 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
Table1. Physicochemical parameters for the BOC Sciences 2D Similarity-based GPCR Focused Screening Library
| Parameter | Value |
| MW | 200-500 |
| ClogP | -1.5-5.5 |
| Number of Rotatable Bonds | ≤9 |
| Number of H Donors | ≤4 |
| Number of H Acceptors | ≤10 |
| TPSA | ≤150 |
| Compounds with ‘undesirable’ functionalities | Removed |
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 2D Similarity-based GPCR Focused Screening Library design at competitive prices for global customers. Personalized and customized services of 2D Similarity-based GPCR Focused Screening 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
- Martins, S.; et al. GPCR screening and drug discovery: Challenges and latest trend. European Pharmaceutical Review. 2012. 17(2).
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