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Updated: Nov 5, 2025

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
Published on: September 9, 2021
Targeting the JAK/STAT Pathway: A Combined Ligand- and Target-Based Approach
Maria Galvez-Llompart1,2, Riccardo Ocello3, Laura Rullo3
1Department of Physical Chemistry, University of Valencia, Av. Vicente Estelles s/n, 46100 Burjassot (Valencia), Spain.
Abstract:
Janus kinases (JAKs) are a family of proinflammatory enzymes able to mediate the immune responses and the inflammatory cascade by modulating multiple cytokine expressions as well as various growth factors. In the present study, the inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway is explored as a potential strategy for treating autoimmune and inflammatory disorders. A computationally driven approach aimed at identifying novel JAK inhibitors based on molecular topology, docking, and molecular dynamics simulations was carried out. For the best candidates selected, the inhibitory activity against JAK2 was evaluated in vitro. Two hit compounds with a novel chemical scaffold, 4 (IC50 = 0.81 μM) and 7 (IC50 = 0.64 μM), showed promising results when compared with the reference drug Tofacitinib (IC50 = 0.031 μM).
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