Name | Doramapimod |
Synonyms | CS-379 CS-1863 BIRB 796 BIRB796 BIBR-796 BIRB-796 Doramapimod 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholinoethoxy)-1-naphthyl]urea 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea 1-[2-(4-Methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea 1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-{4-[2-(morpholin-4-yl)ethoxy]naphthalen-1-yl}urea 1-(3-(1,1-Dimethylethyl)-1-(4-methylphenyl)-1H-pyrazol-5-yl)-3-(4-(2-(morpholin-4-yl)ethoxy)naphthalen-1-yl)urea |
CAS | 285983-48-4 |
EINECS | 1308068-626-2 |
InChI | InChI=1/C31H37N5O3/c1-22-9-11-23(12-10-22)36-29(21-28(34-36)31(2,3)4)33-30(37)32-26-13-14-27(25-8-6-5-7-24(25)26)39-20-17-35-15-18-38-19-16-35/h5-14,21H,15-20H2,1-4H3,(H2,32,33,37) |
Molecular Formula | C31H37N5O3 |
Molar Mass | 527.66 |
Density | 1.20±0.1 g/cm3(Predicted) |
Melting Point | 142-143 °C |
Boling Point | 631.6±55.0 °C(Predicted) |
Flash Point | 335.8°C |
Solubility | Soluble in DMSO (~25 mg/ml), water (poorly soluble), ethanol (~3 mg/ml), and DMF (~25 |
Vapor Presure | 7.36E-16mmHg at 25°C |
Appearance | solid |
Color | White or off-white |
pKa | 13.47±0.70(Predicted) |
Storage Condition | Sealed in dry,Store in freezer, under -20°C |
Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months. |
Refractive Index | 1.619 |
Use | A p38α MAPK and JNK2 |
In vitro study | BIRB 796 acts on ERK-1,SYK,IKK2β,ZAP-70,EGFR kinase, HER2, protein kinase A(PKA),PKC,PKC-α,PKC-β(I and II) and PKC-γ had no significant inhibitory effect. The BIRB 796 significantly increases affinity by forming a hydrogen bond between the morpholine oxygen and the ATP-binding domain of p38α. The BIRB 796 is one of the most potent and slowest isolated inhibitors of p38 MAPK in humans. BIRB 796 effectively inhibit c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. High concentrations of BIRB796 also inhibited the activity and activation of SAPK3/p38γ. BIRB796 blocks pressure-induced phosphorylation of the framework protein SAP97, a substrate for SAPK3/p38γ. BIRB796 acts on HEK293 cells and blocks JNK1/2 activation and activity, while it acts on Hela cells and does not inhibit ERK1/ERK2 activation and activity. Furthermore, binding of BIRB796 to p38 MAPKs or JNK1/2 decreased upstream kinase MKK6 or MKK4 phosphorylation without enhancing dephosphorylation. BIRB 796 acts on BMSCs induced by TNF-α and TGF-β1 and down-regulates IL-6 and VEGF secretion. BIRB-796 has a pyrazole ring, the lipophilic terminal isobutyl group binds to the low selectivity site, and the tolyl ring binds to the high selectivity site. BIRB-796 also inhibited B- Raf and Abl with IC50 of 83 nM and 14.6 μm, respectively. |
In vivo study | BIRB 796 at a dose of 30 mg/kg inhibited TNF-α by 84% in LPS-stimulated mice. It shows high efficacy in rats with collagen-induced arthritis. BIRB 796 oral treatment to rats, with good pharmacokinetic characteristics. |