Kamenecka, Ted published the artcileStructure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38, Category: chlorides-buliding-blocks, the main research area is structure activity aminopyrazole indazole preparation crystal structure JNK3 p38.
C-Jun N-terminal kinase 3α1 (JNK3α1) is a mitogen-activated protein kinase family member expressed primarily in the brain that phosphorylates protein transcription factors, including c-Jun and activating transcription factor-2 (ATF-2) upon activation by a variety of stress-based stimuli. In this study, we set out to design JNK3-selective inhibitors that had >1000-fold selectivity over p38, another closely related mitogen-activated protein kinase family member. To do this we employed traditional medicinal chem. principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC50 = 7 nM) with >2800-fold selectivity over p38 (p38 IC50 > 20 μM) and had cell-based potency of ∼1 μM. In contrast, indazole-based inhibitors exemplified by SR-3737 were potent inhibitors of both JNK3 (IC50 = 12 nM) and p38 (IC50 = 3 nM). These selectivity differences between the indazole class and the aminopyrazole class came despite nearly identical binding (root mean square deviation = 0.33 Å) of these two compound classes to JNK3. The structural features within the compounds giving rise to the selectivity in the aminopyrazole class include the highly planar nature of the pyrazole, N-linked Ph structures, which better occupied the smaller active site of JNK3 compared with the larger active site of p38.
Journal of Biological Chemistry published new progress about Crystal structure. 1095274-55-7 belongs to class chlorides-buliding-blocks, name is Ethyl 3-bromo-5-chlorobenzoate, and the molecular formula is C9H8BrClO2, Category: chlorides-buliding-blocks.
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Chlorides – an overview | ScienceDirect Topics