| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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Purity: ≥98%
| Targets |
p38α (IC50 = 38 nM); p38β (IC50 = 65 nM); p38δ (IC50 = 520 nM); p38γ (IC50 = 200 nM); B-Raf (IC50 = 83.4 nM); Abl (IC50 = 14600 nM); p38 MAP kinase (Kd = 0.1 nM)
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| ln Vitro |
BIRB 796 shows no significant inhibition to ERK-1, SYK, IKK2β, ZAP-70, EGF receptor kinase, HER2, protein kinase A (PKA), PKC, PKC-α, PKC-β (I and II) and PKC-γ. By forming a hydrogen bond between the morpholine oxygen and the ATP-binding domain of p38α, BIRB 796 significantly raises binding affinity. The inhibitor of the human p38 MAP kinase, BIRB 796, is one of the most effective and slowly dissociating inhibitors currently available. [1]
BIRB 796 potently inhibits c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. [2]
In addition, BIRB796 inhibits SAPK3/p38γ activity and activation at a higher concentration than it does for p38α. The scaffold protein SAP97, a physiological substrate of SAPK3/p38γ, is phosphorylated under stressful conditions, but BIRB796 prevents this from happening. In HEK293 cells, BIRB796 inhibits JNK1/2 activation and activity, but it has no effect on ERK1/ERK2 activation or activity in Hela cells. Additionally, rather than promoting dephosphorylation, the binding of BIRB796 to the p38 MAPKs or JNK1/2 inhibits their phosphorylation by the upstream kinases MKK6 or MKK4. [3]
By blocking both baseline and bortezomib-induced upregulation of p38 MAPK and Hsp27 phosphorylation, BIRB 796 increases cytotoxicity and caspase activation. BMSCs stimulated by TNF-α and TGF-β1 secrete IL-6 and VEGF, which are downregulated by BIRB 796. [4]
The pyrazole scaffold of BIRB-796 places a lipophilic t-butyl group in the lower selectivity site and a tolyl ring in the upper selectivity site. Additionally, BIRB-796 inhibits B-Raf and Abl with IC50 values of 83 nM and 14.6 μM, respectively. [5]
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| ln Vivo |
BIRB 796 (30 mg/kg) inhibits 84% of TNF-α in mice stimulated with LPS, and it shows effectiveness in a mouse model of collagen-induced arthritis. [1]
BIRB 796 BIRB 796 exhibits good pharmacokinetic performance even after oral administration in mice. [2]
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| Enzyme Assay |
THP-1 cells are preincubated for 30 min. both with and without BIRB 796. LPS is added to the cell mixture in a final concentration of 1 μg/mL, and the above-mentioned incubation is carried out overnight (18–24 hours). A commercially available ELISA is used to check the supernatant for human TNF-α. An EC50 value is calculated by combining the data and performing nonlinear regression analysis using a three parameter logistic model. In each experiment, BIRB 796 is examined, and the 95% confidence intervals for the EC50 range from 16 to 22 nM.
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| Cell Assay |
Human embryonic kidney (HEK) 293 and HeLa cells are exposed to 0.5 M sorbitol for 30 min or 100 ng/mL EGF for 10 min and then lysed in buffer A (50 mM Tris-HCl, pH 7.5, 1 mM EGTA, 1 mM EDTA, 1 mM sodium orthovanadate, 10 mM sodium fluoride, 50 mM sodium β-glycerophosphate, 5 mM pyrophosphate, 0.27 M sucrose, 0.1 mM phenylmethylsulfonyl fluoride, 1% (v/v) Triton X-100) plus 0.1% (v/v) 2-mercaptoethanol and Complete proteinase inhibitor mixture. The supernatants are removed from the lysates after being centrifuged at 18,000× g for 5 min at 4°C. They are then quickly frozen in liquid nitrogen and kept at -20°C until needed. Whenever necessary, cells are pre-incubated for 1 hour with or without 10 μM SB 203580, 10 μM PD 184352, or with various concentrations of Doramapimod for the durations shown in the figures.
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| Animal Protocol |
Mice: The animals are 6- to 8-week-old athymic nude mice (BALB/c-nu/nu), weighing 18 to 24 g. Doramapimod (10 mg/kg p.o., every 3 days×5) is given to the mice as a treatment. Every three days, the animal weights, the diameters of the two perpendicular tumors (A and B), and the estimated tumor volume (V) are all recorded.
Rats: Age-matched nontransgenic Sprague-Dawley (SD) rats (MDC) and male transgenic dTGRs (RCC Ltd) are used. There are two different protocols used. In protocol 2, rats from the untreated dTGR (n=15), dTGR+BIRB796 (n=11) and SD (n=8 each group) groups are examined. Every week, a tail cuff is used to measure systolic blood pressure. In metabolic cages, 24-hour urine samples are taken from weeks 5 to 7. At week 7, serum is collected. Clinical standard assays are used to measure serum creatinine and cystatin C. Enzyme-linked immunosorbent assay is used to measure the albumin content of rat urine. Protocol 2 aims to concentrate on electrophysiological changes and mortality. Up to week 8, untreated dTGR (n = 10), dTGR+BIRB796 (n = 10), and SD (n = 10) rats are investigated. |
| References |
| Molecular Formula |
C31H37N5O3
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|---|---|---|
| Molecular Weight |
527.66
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| Exact Mass |
527.29
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| Elemental Analysis |
C, 70.56; H, 7.07; N, 13.27; O, 9.10
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| CAS # |
285983-48-4
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| Related CAS # |
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| Appearance |
White to gray solid powder
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| LogP |
5.7
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| tPSA |
80.6Ų
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| SMILES |
CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5
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| InChi Key |
MVCOAUNKQVWQHZ-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea
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| Synonyms |
BIRB796; BIRB-796; Doramapimod; BIRB 796; BIRB0796; BIRB-0796
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8952 mL | 9.4758 mL | 18.9516 mL | |
| 5 mM | 0.3790 mL | 1.8952 mL | 3.7903 mL | |
| 10 mM | 0.1895 mL | 0.9476 mL | 1.8952 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02211885 | Completed | Drug: 14C-BIRB 796 BS | Healthy | Boehringer Ingelheim | October 2002 | Phase 1 |
| NCT02211144 | Completed | Drug: BIBR 796 BS Drug: Placebo |
Healthy | Boehringer Ingelheim | March 2002 | Phase 1 |
| NCT02211157 | Completed | Drug: BIBR 796 BS Drug: Placebo |
Healthy | Boehringer Ingelheim | March 2000 | Phase 1 |
| NCT02209779 | Completed | Drug: BIBR 796 BS Drug: Placebo |
Arthritis, Rheumatoid | Boehringer Ingelheim | May 2001 | Phase 2 |
| NCT02209831 | Completed | Device: BIBR 796 BS Drug: Pantoprazole |
Healthy | Boehringer Ingelheim | November 2001 | Phase 1 |
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