Currently, 49 members of the nuclear receptor superfamily have been identified, which not only provide a large number of targets for drug development, but are also very successfully developed in drug therapy. With years of experience, we provide customized structure-based nuclear receptors modeling service to precisely meet customer requirements.

Introduction of Structure-Based Nuclear Receptors Modeling

Nuclear receptors (NRs) are proteins that bind steroids and thyroid hormones to regulate gene expression to control cellular homeostasis, development, and metabolism. Given the broad roles and physiological importance of NRs, this target family is a potential target for therapeutic approaches in many clinical conditions, including cancer, diabetes, and neurological disorders. It is found that the nuclear receptor superfamily consists of 49 identified proteins, of which 24 proteins have known ligands, and the remaining 25 proteins have not yet been identified. The development of small molecules targeting nuclear receptors is a challenging task, considering not only high-affinity binding but also aspects such as nuclear localization or transactivation effects of target proteins. Therefore, designing molecules that selectively activate or inhibit specific NRs is of considerable biological interest and may have the potential for important clinical applications.

Fig 1. A Virtual Screening scheme for NRs. (Ai N, et al., 2009)

Services

The transcriptional activity of NR is guided by interactions with ligands and various cofactor proteins. In recent years, computational models of NR have proven increasingly valuable for advancing the understanding of NR pharmacology. Creative BioMart is committed to building structure-based NR drug discovery platforms designed to understand and mimic the functional activity of NR modulators at the molecular level. Here, we can help your project identify synthetic compounds that mimic the activity of cognate NR ligands, and the development of synthetic compounds that selectively modulate the pharmacology of NR in a cell-type and/or tissue-selective manner to deliver desired therapeutic effects while avoiding potentially undesirable off-target effects. We provide structure-based NRs modeling services for a variety of diseases (such as cancer, inflammation, neurological diseases, metabolic diseases, etc.), the main process is as follows:

(1) Virtual screening to identify NR modulators.

(2) Calculate the toxicity profile associated with NR modulators.

Approaches of Structure-Based Nuclear Receptors Modeling

We have discovered many agonists and antagonists for NR through the following computational methods, which are widely used to advance the understanding of various aspects of NR pharmacology.

• Ligand-based method: this method mainly focuses on molecular similarity. This is a particularly valuable method for identifying compounds if structural information on the receptor is not available.
• Receptor-based method: this method primarily generates three-dimensional structures of protein targets from X-ray crystallography, NMR structures, or homology modeling to resolve potential ligands that may bind to receptors.

Creative BioMart is committed to providing global customers with high-quality structure-based nuclear receptors modeling service to develop improved modulators of NRs for receptors targeted by approved drugs and also intend to address other NRs in various diseases for which agonists or antagonists have been identified. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

References

1. Ai N, Krasowski M D, Welsh W J, et al.. (2009) Understanding nuclear receptors using computational methods[J]. Drug discovery today. 14(9-10): 486-494.
2. Kronenberger T, Keminer O, Wrenger C, et al.. (2015) Nuclear receptor modulators—current approaches and future perspectives[J]. Drug Discovery and Development–From Molecules to Medicine.

• Computational Design of Protein-Protein Interactions
• Computer Prediction of Drug Metabolism Service
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