Antibodies
BIRB 796 (Doramapimod)
- 貨號 Cat. No.
- S1574
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
BIRB 796 (Doramapimod)
BIRB 796 (Doramapimod) is a highly selective p38α MAPK inhibitor with Kd of 0.1 nM, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2, ZAP-70, EGFR, HER2, PKA, PKC, PKCα/β/γ.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | BIRB 796 (Doramapimod) is a highly selective p38α MAPK inhibitor with Kd of 0.1 nM, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2, ZAP-70, EGFR, HER2, PKA, PKC, PKCα/β/γ. | |||||
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| Targets | p38α MAPK | |||||
| IC50 | 0.1 nM (Kd) [1] | |||||
| In 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. BIRB 796 greatly improves binding affinity by forming a hydrogen bond between the morpholine oxygen and the ATP-binding domain of p38α. BIRB 796 represents one of the most potent and slowest dissociating inhibitors against human p38 MAP kinase now known. [1] BIRB 796 potently inhibits c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. [2] BIRB796 also inhibits the activity and the activation of SAPK3/p38γ at a higher concentration than it does in p38α. BIRB796 blocks the stress-induced phosphorylation of the scaffold protein SAP97, which is a physiological substrate of SAPK3/p38γ. BIRB796 blocks JNK1/2 activation and activity in HEK293 cells, while not inhibits the activation and activity of ERK1/ERK2 in Hela cells. Moreover, the binding of BIRB796 to the p38 MAPKs or JNK1/2 is impairing their phosphorylation by the upstream kinase MKK6 or MKK4 rather than enhancing their dephosphorylation. [3]BIRB 796 blocks baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. BIRB 796 downregulates IL-6 and VEGF secretion in BMSCs triggered by TNF-α and TGF-β1. [4] BIRB-796 has a pyrazole scaffold that places a lipophilic t-butyl group into the lower selectivity site and a tolyl ring into the upper selectivity site. BIRB-796 also inhibits B-Raf and Abl with IC50 of 83 nM and 14.6 μM, respectively. [5] | |||||
| In vivo | BIRB 796 (30 mg/kg) inhibits 84% of TNF-α in LPS-stimulated mice and demonstrates efficacy in a mouse model of established collagen-induced arthritis. [1] BIRB 796 has good pharmacokinetic performance even after oral administration in mice. [2] | |||||
| Features | The first p38 MAPK inhibitor to be tested in a phase III clinical trial. | |||||
Protocol(Only for Reference)
Kinase Assay: [6]
| Procedures for the THP-1 cellular assay for inhibition of LPS-stimulated TNF-α production | THP-1 cells are preincubated in the presence and absence of BIRB 796 for 30 min. Cell mixture is stimulated with LPS (1 μg/mL final) and incubation continued overnight (18−24 hours) as above. Supernatant is analyzed for human TNF-α by a commercially available ELISA. Data are combined and analyzed by nonlinear regression using a three parameter logistic model to obtain an EC50 value. BIRB 796 is analyzed in each experiment and the 95% confidence intervals for the EC50 are between 16 and 22 nM. |
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Animal Study: [2]
| Animal Models | Collagen-induced arthritis in female Balb/c mice |
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| Dosages | 1 mg/kg (intravenous) or 10 mg/kg (oral) |
| Administration | Intravenous injection or by oral |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL |
References
Chemical Information
Download BIRB 796 (Doramapimod) SDF
| Molecular Weight (MW) | 527.66 |
|---|---|
| Formula | C31H37N5O3 |
| CAS No. | 285983-48-4 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 106 mg/mL (200 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 106 mg/mL (200 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.52766 | 5.2766 | 10.5532 | 15.8298 |
Customer Reviews (1)
 Click to enlarge | Rating | |
| Source | BIRB 796 (Doramapimod) purchased from Selleck | |
| Method | Western blot | |
| Cell Lines | HEK293 cells | |
| Concentrations | 0.01-1 μM | |
| Incubation Time | 1 h | |
| Results | BIRB796 treatment resulted in a reduction of p38 phosphorylation in HEK293 cells. |
Product Citations (7)
RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion. [Baudet A, et al. Blood 2012;119(26):6255-8]
Novel function for the p38-MK2 signalling pathway in circulating CD1c+ (BDCA-1+) myeloid dendritic cells from healthy donors and advanced cancer patients; inhibition of p38 enhances IL-12 whilst suppressing IL-10. [Franks HA, et al. Int J Cancer 2013;134(3):575-86]
Glucose induces autophagy under starvation conditions by a p38 MAPK-dependent pathway. [Moruno-Manchón JF, et al. Biochem J 2013;449(2):497-506]
