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logical systems and cell lines. This compound showed inhibition of
the JAK3 phosphorylation substrate STAT5 in T-cells and potent
activity in mast cells preventing chemotaxis. Furthermore, it
showed potent activity in vivo lowering biomarkers of increased
JAK3 activity, including IgE and asthmatic responses.
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The authors would like to thank Dave Ritchie on the Biology
support team for PK evaluation, and Kenneth Wells on the HOPS
team for scale up of compound 32.
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Supplementary data
Supplementary data (synthetic procedures and characterization
data for most compounds are provided, along with procedures for
the some biological assays and animal experiments) associated
with this article can be found, in the online version, at
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References and notes
20. Compound 32 was docked into JAK3 using the docking program Glide (Glide,
Schrodinger, 1500 S.W. First Ave., Suite 1180, Portland, OR 97201). The
molecular mechanism calculations were done with MacroModel (MacroModel,
Schrodinger, 1500 S.W. First Ave., Suite 1180, Portland OR 97201), using
OPLS2001 force field. The effect of aqueous solution was treated by GB/SA
model. Polak-Ribiere conjugate gradient method was used for energy
minimization, and the derivative convergence criterion was set at 0.05 KJ/A-
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