Doramapimod (BIRB 796), a pan p38 MAPK inhibitor, acts on p38α/β/γ/δ in cell-free assays with IC50 of 38 nM, 65 nM, 200 nM, and 520 nM, respectively, and binds to p38α. The Kd in THP-1 cells is 0.1 nM, which is 330 times more selective than JNK2, and has weak inhibitory effect on c-RAF, Fyn and Lck, as well as weak inhibitory effect on ERK-1, SYK and IKK2.

 

Brand: BCM

 

Target: Raf; Autophagy; p38 MAPK

 

Signaling Pathways: Autophagy; MAPK

 

In Vitro: Doramapimod (BIRB796) is a highly potent inhibitor of p38 MAPK (Kd: 0.1 nM) that blocks TNFα release in LPS-stimulated THP-1 cells (IC50: 18 nM) . BIRB796 also inhibits the activity and the activation of SAPK3/p38gamma. BIRB796 blocks the stress-induced phosphorylation of the scaffold protein SAP97. BIRB 796 inhibited Hsp27 phosphorylation induced by 17-AAG plus bortezomib, thereby enhancing cytotoxicity. In bone marrow stromal cells (BMSC), BIRB 796 inhibited phosphorylation of p38 MAPK and secretion of IL-6 and vascular endothelial growth factor triggered by either tumour necrosis factor-alpha or tumour growth factor-beta1. BIRB 796 also inhibited IL-6 secretion induced in BMSCs by adherence to MM cells, thereby inhibiting tumour cell proliferation.

 

In Vivo: Systolic blood pressure of untreated dTGRs was 204 mm Hg, but partially reduced after BIRB796 (30 mg/kg per day) treatment (166 mm Hg), whereas Sprague-Dawley rats were normotensive. The beta-myosin heavy chain expression of BIRB796-treated hearts was significantly lower in BIRB796 compared with dTGRs. BIRB796 treatment significantly reduced cardiac fibrosis, connective tissue growth factor, tumor necrosis factor-alpha, interleukin-6, and macrophage infiltration.

 

Melting Point: 142-143 °C

 

Boiling Point: 631.6±55.0 °C at 760 mmHg

 

Flash Point: 335.8±31.5 °C

 

Vapour Pressure: 0.0±1.9 mmHg at 25°C

 

pKa: 13.47±0.70(Predicted)

 

Solubility: Soluble in DMSO; soluble in Ethanol. Insoluble in Water.

 

GHS: GHS07

 

Isomeric SMILES: CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5  

 

InChIKey: MVCOAUNKQVWQHZ-UHFFFAOYSA-N  

 

InChI: InChI=1S/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)

 

Attribute
[Chem Name]	1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea
[Synonym]	Doramapimod; BIRB 796; BIRB-796
[CAS No.]	285983-48-4
[EINECS]	1308068-626-2
[MDL No.]	MFCD09752957
[Formula]	C31H37N5O3
[Molecular]	527.66
[Form]	White to off-white powder
[Storage]	Sealed in dry. Store in freezer, under -20°C

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