{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kamenecka T"],"funding":["NINDS NIH HHS"],"pagination":["12853-61"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2676016"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["284(19)"],"pubmed_abstract":["c-Jun N-terminal kinase 3alpha1 (JNK3alpha1) 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 chemistry principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC(50) = 7 nm) with >2800-fold selectivity over p38 (p38 IC(50) > 20 microm) and had cell-based potency of approxim"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-Jun N-terminal kinase 3 (JNK3) over p38."],"pmcid":["PMC2676016"],"funding_grant_id":["U01-NS057153"],"pubmed_authors":["Habel J","Kamenecka T","Chen W","LoGrasso P","Ling YY","Jiang R","Duckett D","Song X","Frackowiak B","Shin Y"],"additional_accession":[]},"is_claimable":false,"name":"Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-Jun N-terminal kinase 3 (JNK3) over p38.","description":"c-Jun N-terminal kinase 3alpha1 (JNK3alpha1) 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 chemistry principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC(50) = 7 nm) with >2800-fold selectivity over p38 (p38 IC(50) > 20 microm) and had cell-based potency of approxim","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 May","modification":"2026-04-18T11:10:25.63Z","creation":"2019-03-27T00:22:06Z"},"accession":"S-EPMC2676016","cross_references":{"pubmed":["19261605"],"doi":["10.1074/jbc.m809430200","10.1074/jbc.M809430200"]}}