| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1993296 | Methods | 2015 | 5 Pages |
•High-throughput virtual screening was applied to a natural product database.•Emodic acid and 6-chloroemodic acid were identified as inhibitors of JAK2.•The compounds inhibited JAK2 activity in vitro and in cellulo.•The inhibition of STAT3 DNA-binding activity in nuclear extracts was demonstrated.
Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.
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