JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules.

A competitive fluorescence polarization (FP) assay is reported for determining binding affinities of probe molecules with the pseudokinase JAK2 JH2 allosteric site. The syntheses of the fluorescent 5 and 6 used in the assay are reported as well as Kd results for 10 compounds, including JNJ7706621, NVP-BSK805, and filgotinib (GLPG0634). X-ray crystal structures of JAK2 JH2 in complex with NVP-BSK805, filgotinib, and diaminopyrimidine 8 elucidate the binding poses.

Citation

Ana S Newton, Luca Deiana, David E Puleo, José A Cisneros, Kara J Cutrona, Joseph Schlessinger, William L Jorgensen. JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules. ACS medicinal chemistry letters. 2017 Jun 08;8(6):614-617

PMID: 28626520

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