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BIRB796 is a highly potent inhibitor of p38 MAPK that enhances stem cell activity of cultured umbilical cord blood-derived hematopoietic cells. BIRB796 can be used in protocols for the chemical reprogramming of somatic cells to iPSCs.
BIRB796 (Doramapimod) is an orally active, highly potent p38 MAPK inhibitor, which has an IC50 for p38α=38 nM, for p38 β=65 nM, for p38γ=200 nM, and for p38δ=520 nM. BIRB796 has picomolar affinity for p38 kinase (Kd=0.1 nM) and inhibits B-Raf with an IC50 of 83 nM1,2. BIRB796 is usually associated with inflammation because of its role in T-cell proliferation and cytokine production. BIRB796 blocks the stress-induced phosphorylation of the scaffold protein SAP97, further establishing that this is a physiological substrate of SAPK3/p38γ. The binding of Doramapimod to the p38 MAPKs or JNK1/2 is impairing their phosphorylation by the upstream kinase MKK6 or MKK4.
In research applications, BIRB796 has been shown to rescue the self-renewal ability of muscle satellite cells (Bernet et al.), increase the regenerative capacity of functional aged skeletal muscle stem cells (Cosgrove et al.), and block GADD45G-induced differentiation of long-term repopulating hematopoietic stem cells (Thalheimer et al.).
Description: High affinity and selective p38 kinase inhibitor Alternative Names: Doramapimod, p38 MAP Kinase Inhibitor X Chemical Name: Urea, N-[3-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H-pyrazol-5-yl]-N'-[4-[2-(4- morpholinyl)ethoxy]-1-naphthalenyl] Purity: ≥ 98% by NMR
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