Docking-based Nuclear Receptor Library

Nuclear Receptor(NR) is a transcription factor that is naturally turned on and off by small molecule hormones. These hormones often have physicochemical properties very similar to those of therapeutic chemical entities. Therefore, NR represents an important class of drug targets with potential applications in cancer, inflammatory diseases and diabetes. Several drugs targeting at different NRs, such as tamoxifen (a partial antagonist of the estrogen receptor (ER)) or bicalutamide (an antagonist of androgen receptor (AR) used in the treatment of breast and prostate cancers), are already available on the market, and the number of high-quality crystal structures of ligand-binding domains of many important nuclear receptor is currently in a rapid growth phase, which also creates the opportunity for structure-based identification of potential nuclear receptor agonists, antagonists or tissue-selective modulators. antagonists or tissue-selective modulators based on structure.

BOC Sciences can create a comprehensive docking-based nuclear receptor library consisting of different types of human NRs, and our teams have tested the ability to identify their ligands in virtual screening campaigns, as well as predict their binding geometry, functional type and relative binding affinity.

Figure 1. Molecular modelling of docking of mifepristone analogues to the progesterone receptor ligand binding domain. (DeBono, A.; et al. 2019)

Docking-based Nuclear Receptor Library Design

1. Firstly, a in silico pre-screening against all compounds in BOC Sciences HTS compound collection has delivered the selection of approximately 5,000 potential nuclear receptor modulators. Among them, molecules with unwanted structures are carefully filtered out.
2. Then, Glide docking is employed in which available crystal structures of multiple nuclear receptors (estrogen, androgen, progesterone, glucocorticoid, saltocorticoid, RAR, RXR, PXR, ROR (-α/γ), LXR, PPAR, thyroid hormone receptor) are utilized
• A diversity of H-bonds and hydrophobic constraints are assigned
• Electrostatic maps of the binding sites are employed as docking/screening models
3. To estimate the efficiency of the docking procedure, a reference set with known nuclear receptor antagonist activity (IC) is used to validate each model
4. Finally, these compounds are ranked according to the docking score values obtained from a docking reference set

Docking-based Nuclear Receptor Library Characteristics

• Our well-designed high quality algorithms can provide accurate ligand binding pose prediction, virtual compound screening and selectivity analysis
• 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 Docking-based Nuclear Receptor Library design at competitive prices for global customers. Personalized and customized services of Docking-based Nuclear Receptor 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!