Researchers at St. Jude Children's Research Hospital have discovered a vinblastine analog with high affinity to the human pregnane X receptor (hPXR) that can be used as a fluorescent probe in assays to study the binding of compound to hPXR. This is the first fluorescent probe for hPXR binding with a disclosed chemical structure. Currently, one company offers a hPXR binding assay kit; but the chemical structure of the hPXR fluorescent probe included in the kit is not disclosed. Knowing the chemical structure is critical to understanding the ligand-PXR interaction, and would make this fluorescent hPXR binding probe preferable.
vinblastine analog, pregnane X receptor (hPXR), fluorescent probe
Granted Patents or Published Applications
Related Scientific References
Lin, Wenwei and Chen, Taosheng, “A Vinblastine Fluorescent Probe for Pregnane X Receptor in a Time-Resolved Fluorescence Resonance Energy Transfer Assay,” Analytical Biochemistry, Sept. 14, 2013
Wenwei Lin , Jiuyu Liu , Cynthia Jeffries , Lei Yang , Yan Lu , Richard E. Lee , and Taosheng Chen , “Development of BODIPY FL Vindoline as a Novel and High-Affinity Pregnane X Receptor Fluorescent Probe,” Bioconjugate Chem., Aug. 11, 2014 http://pubs.acs.org/doi/abs/10.1021/bc5002856
We are looking for a commercial partner to license this discovery and develop PXR binding assay kits and reagents. Binding to hPXR also risks inducing drug-drug interactions and failure of lead compounds in clinical trials; therefore many drug companies have a dedicated group whose function is evaluating the lead compounds' effect on hPXR binding and activation. Other benefits include a probe available in powder form, making it flexible to formulate appropriately and dissolve in solvent, which is important for high throughput screening. This fluorescent hPXR probe can also be used by drug companies in their binding assays to replace radioisotope-based binding assay.
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