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It is a pyrazole-based allosteric inhibitor of p38 MAP Kinase with a Kd of 0.1 nM. BIRB796 has slow binding kinetics, as evidenced by an marked increase in apparent IC50 after preincubation periods up to 2h, as well as dissociation rates of up to six orders of magnitude greater when compared to other MAPK inhibitors. BIRB796 possesses an excellent selectivity profile over a panel of relevant kinases, with the most active being inhibition of JNK2a2 at 100 nM (330-fold selectivity).Related studies have shown that BIRB796 also inhibits activity and activation of SAPK3/p38g (3% remaining activity at 10 uM). At these concentrations, BIRB796 blocks stress-induced phosphorylation of scaffold protein SAP97.
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