The binding mode of JNK-isoform-selective inhibitor 10 within the ATP-binding
site of JNK3 was determined by X-ray experiments (Fig. 11). The R-enantiomer of
10 forms several hydrogen bond interactions with JNK3. The chloro-substituted
phenyl ring is located in the hydrophobic region I. The N2 atom of the central
pyrazole accepts a hydrogen bond from the NH group of Met149 of the hinge region.
Fig. 10 Structural modifications of the lead structure 9 (SR-4326) and structures as well as
biological data of inhibitors 10 and 11 (SR-11935) of this series. Biological data are taken
from Zheng et al. [37]
Fig. 11 X-ray structure of inhibitor 10 in complex with JNK3 (PDB code: 4WHZ). The protein
backbone is displayed as cartoon in gray. The compound and selected amino acids are highlighted
as sticks. Hydrogen bonds are shown as yellow dashed lines
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P. Koch
site of JNK3 was determined by X-ray experiments (Fig. 11). The R-enantiomer of
10 forms several hydrogen bond interactions with JNK3. The chloro-substituted
phenyl ring is located in the hydrophobic region I. The N2 atom of the central
pyrazole accepts a hydrogen bond from the NH group of Met149 of the hinge region.
Fig. 10 Structural modifications of the lead structure 9 (SR-4326) and structures as well as
biological data of inhibitors 10 and 11 (SR-11935) of this series. Biological data are taken
from Zheng et al. [37]
Fig. 11 X-ray structure of inhibitor 10 in complex with JNK3 (PDB code: 4WHZ). The protein
backbone is displayed as cartoon in gray. The compound and selected amino acids are highlighted
as sticks. Hydrogen bonds are shown as yellow dashed lines
214
P. Koch