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.
|Molecular Name||BIRB796 (Doramapimod)|
|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|
|Physical Appearance||White to gray (Solid)|
|Target||p38 MAPK; Raf; Autophagy|
|Storage||Powder: -20°C for 3 years and 4°C for 2 years|
|Quality Statement||This product is for Research Use Only and is not intended for therapeutic or diagnostic use.|
- BIRB796 Technical Data Sheet
- Brochure: Small Molecules for Stem Cell Research
- FAQs: General Guide for Small Molecules
References and Publications
- Dietrich J, et al. The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors. Bioorg Med Chem. 2010 Aug 1;18(15):5738-48
- Cicenas J, et al. JNK, p38, ERK, and SGK1 Inhibitors in Cancer. Cancers (Basel). 2017 Dec 21;10(1). pii: E1.
- Kuma Y, et al. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem, 2005, 280(20), 19472-19479.