Research Area
Product Type
United States ( Change Country )
BIRB 796 (Doramapimod) Chemical Structure
SB 203580
SB 203580 is a potent inhibitor of LPS-induced cytokine synthesis in the human monocyte cell line THP-1 (IC50 = 50-100 nM).
SB 202190
SB 202190 is a P38 MAP(mitogen activated protein) Kinase inhibitor.
VX-745
VX-745 is a potent and selective inhibitor to p38α and p38β MAPK with IC50 of 10 nM and 220 nM, respectively.
LY2228820
LY2228820 is a novel and potent p38MAPK inhibitor (the IC50 for p38αMAPK and p38βMAPK were 7 nM and 3 nM, respectively).
Vinorelbine (Navelbine)
Vinorelbine (Navelbine) is the first 5´NOR semi-synthetic vinca alkaloid and exerts its activity through the MAPK (p38) pathway with median IC90 and IC50 of 15.5 and 2.3 μM.
Asiatic acid
Asiatic acid is the aglycone of asiaticoside isolated from the plant Centella asiatica, commonly used in wound healing.
PH-797804
PH-797804 is a highly selective, potent, and ATP-competitive p38 MAP kinase inhibitor with an IC50 of 2.3 nM.
VX-702
VX-702 is a highly selective, orally active inhibitor of p38 MAPKα with an IC50 range of 4 to 20 nM for human platelets.
AZD6244 (Selumetinib)
AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM.
CI-1040 (PD184352)
CI-1040 (PD184352) is a MEK 1/2 inhibitor. Ki of 300nM
Biological Activity
| Information | BIRB 796 (Doramapimod) is a highly selective p38α MAPK inhibitor of TNF-α with EC50 of 18 nM in THP-1 cells. | |||||
|---|---|---|---|---|---|---|
| Targets | TNF-α | |||||
| IC50 | 18 nM (EC50) [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] | |||||
| Clinical Trials | Boehringer Ingelheim has announced the discontinuation of BIRB 796 R&D project in 2005. | |||||
| Features | BIRB 796 is the first p38 MAPK inhibitor to reach phase III clinical trial. | |||||
Protocol
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. |
|---|
Animal Study:[2]
Product Information
| Molecular Weight (WM): | 527.66 |
|---|---|
| Formula: | C31H37N5O3 |
| CAS No.: | 285983-48-4 |
| Synonyms: |
N/A
|
| Dissolve in (25°C): | DMSO ≥106mg/mL |
| Water <1mg/mL | |
| Ethanol ≥106mg/mL | |
| Storage: | 2 years-20°CPowder |
| 1 week-4°Cin DMSO | |
| 1 month-80°in DMSO |
Quality Control & MSDS
Research Area
Notes:
Related Inhibitors
Recommended Screening Libraries
Chemical Library
A collection of 864 bioactive compounds
Inhibitor Library
A collection of 481 inhibitors
Kinase Inhibitor Library
A collection of 194 kinase inhibitors
Tyrosine Kinase Inhibitor Library
A collection of 85 tyrosine kinase inhibitors.
FDA Approved Drug Library
A collection of 426 FDA approved drugs
Natural Product Library
A collection of 139 natural products
Chemotherapeutic Agent Library
A collection of 40 chemotherapeutic agents
Epigenetics Compound library
A unique collection of 17 small molecule modulators
Stem Cell Compound library
A unique collection of 47 small molecule inhibitors
GPCR Compound library
A unique collection of 63 GPCR small molecules
Keywords:buy BIRB 796 (Doramapimod) | BIRB 796 (Doramapimod) supplier | purchase BIRB 796 (Doramapimod) | BIRB 796 (Doramapimod) cost | BIRB 796 (Doramapimod) manufacturer | order BIRB 796 (Doramapimod) | BIRB 796 (Doramapimod) distributor