Nuclear Receptors Assays

Nuclear receptors are ligand-inducible transcriptional factors that control multiple biological phenomena, including proliferation, differentiation, reproduction, metabolism, and the maintenance of homeostasis. Members of the nuclear receptor superfamily have marked structural and functional similarities, and their domain functionalities and regulatory mechanisms have been well studied. Various modulators of nuclear receptors, including agonists and antagonists, have been developed as tools for elucidating nuclear receptor functions and also as drug candidates or lead compounds. ER(Estrogen receptor, ERα: NR3A1, ERβ: NR3A2), AR(Androgen receptor: NR3C4), and PPARs(Peroxisome proliferator activated receptor, PPARα: NR1C1, PPARβ/δ: NR1C2, and PPARγ: NR1C3) are major targets for chemical screening. Nuclear receptors are successfully targeted in the clinic to treat, for example, cancer, cardiovascular or autoimmune diseases. Many assay systems are currently available to evaluate the modulation of nuclear receptor functions, and are useful as screening tools in the discovery and development of new modulators.

Figure 1 Nuclear Receptors

The ability to discover active compounds in a chemical library depends largely on the efficiency and robustness of the assay method used in the chemical screening, and also on the selection criteria for the chemical library. Assay methods used to evaluate nuclear receptors can be classified into two types: one is target-based chemical screening, which involves the direct observation of the interaction between the ligand and the target receptor, or the conformational changes of the target receptor, or the changes in transcriptional activity, and the other is phenotypic chemical screening.

CD ComputaBio offers a suite of assays to support the discovery of new drugs to modulate nuclear receptors with the following advantages:

• Cell-based assays allow for drug testing in the physiological and complex environment of intact cells.
• Luciferase reporter assay format measures the activity of the nuclear receptors on the target gene expression, therefore, a large variety of drugs can be tested such as modulators of translocation, activity, structural changes, dimerization, etc.
• High-throughput screening-focused devices.
• Both low and large-scale drug screening is available.
• In silico screening based on increasing amounts of protein structure data and protein-ligand docking simulations.
• Fast turnaround time: Complete your project within 2-3 weeks. Expedited scheduling and data delivery can be arranged.
• Report: A detailed report including assay conditions and comprehensive evaluation of data for each analysis will be provided.

In silico screening, also called virtual screening, is a computer simulation method to select compounds that are predicted to interact with a target protein. In addition to in-house libraries (tens of thousands to millions of compounds) owned by companies and research institutes, commercially available compounds are also used for in silico screening. Furthermore, in silico screening can cover the compounds never synthesized or isolated, which can be constructed according to the purpose of the screening. Thus, the likelihood of discovering active compounds has been rapidly increasing. Machine-learning methods can be useful for predicting the biological effects of candidate compounds for modulating nuclear receptors. If you have any special requirements in Nuclear Receptor Assays, please contact us at any time. We are looking forward to working together with your attractive projects.