| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
MEK5 (IC50 = 1.5 nM); ERK5 (IC50 = 59 nM)
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| ln Vitro |
BIX02189 blocks MEK5 and ERK5 catalytic activity with IC50 values of 1.5 nM and 59 nM, respectively. With IC50 values of 4.3 nM and 810 nM, respectively, they are more potent than the effect brought on by BIX02188. BIX02189 exhibits inhibitory activity against CSF1R (FMS) with an IC50 of 46 nM but exhibits no activity against related kinases MEK1, MEK2, ERK1, p38α, JNK2, EGFR, and STK16 with IC50 values of >3.7 μM. Pretreatment with BIX02189 inhibits sorbitol-induced ERK5 phosphorylation in HeLa cells in a dose-dependent manner but has no inhibitory effect on ERK1/2, p38, or JNK1/2 MAPK phosphorylation. In HeLa or HEK293 cells, BIX02189 treatment alone for 24 hours had no cytotoxic effects. In HeLa and HEK293 cells, BIX02189 inhibits MEK5/ERK5/MEF2C-driven luciferase expression with IC50 values of 0.53 μM and 0.26 μM, respectively. This has a greater impact than what BIX02188 has to offer. [1] In human umbilical vein endothelial cells (HUVECs) exposed to 15d-PGJ2, BIX02189 reverses the protective effect brought on by laminar flow (L-flow) by suppressing C-terminus of Hsc70-interacting protein (CHIP)-mediated p53 ubiquitination. [2] In neonatal rat cardiomyocytes (NRCMs) stimulated by isoproterenol, BIX02189 (10 uM) inhibits ERK5 phosphorylation and decreases myocyte enhancer factor 2 (MEF2) transcriptional activity. By accelerating sorbitol-induced apoptosis in NRCMs, BIX02189 supports the protective function of ERK5 in cardiomyocytes. [3]
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| ln Vivo |
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| Enzyme Assay |
Utilizing the PKLight ATP Detection Reagent, the MEK5 protein isolated from the baculovirus expression system is used to assess kinase activity. The assay is carried out in the presence of varying concentrations of BIX02189 using 15 nM GST-MEK5 and 0.75 μM ATP in an assay buffer made up of 25 mM Hepes, pH 7.5, 10 mM MgCl2, 50 mM KCl, 0.2% BSA, 0.01% CHAPS, 100 μM Na3VO4, 0.5 mM DTT, and 1% DMSO. The kinase reaction mixture is incubated for 90 minutes at room temperature before 10 μL of ATP detection reagent is added. For the purpose of determining the IC50 value, the relative light unit (RLU) signal is measured and converted to percent of control (POC) values.
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| Cell Assay |
Before being stimulated with sorbitol at a final concentration of 0.4 M for 20 minutes at 37 °C, the cells are serum-starved for 20 hours. 1.5 hours go by between the addition of BIX02189 and the sorbitol. At 4 °C for 5 to 10 minutes, the cells are collected and lysed in 50 μL of RIPA buffer containing Halt protease and phosphate inhibitors. The lysates are centrifuged at 14,000 rpm for 10 minutes, and then 50 μL of the lysate is mixed with 50 μ 2× sample buffer and boiled at 95 °C for 4 minutes. A sample of 20 microliters is run on 10% Tris-glycine SDS-PAGE gels before being transferred to nitrocellulose. With the appropriate antibodies, western blotting is carried out.
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| Animal Protocol |
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| References |
| Molecular Formula |
C27H28N4O2
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|---|---|
| Molecular Weight |
440.54
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| Exact Mass |
440.22
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| Elemental Analysis |
C, 73.61; H, 6.41; N, 12.72; O, 7.26
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| CAS # |
1094614-85-3
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| Related CAS # |
BIX02189;1265916-41-3
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| Appearance |
Solid powder
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| SMILES |
CN(C)CC1=CC(=CC=C1)N=C(C2=CC=CC=C2)C3=C(NC4=C3C=CC(=C4)C(=O)N(C)C)O
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| InChi Key |
ZGXOBLVQIVXKEB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28N4O2/c1-30(2)17-18-9-8-12-21(15-18)28-25(19-10-6-5-7-11-19)24-22-14-13-20(27(33)31(3)4)16-23(22)29-26(24)32/h5-16,29,32H,17H2,1-4H3InChI=1S/C27H28N4O2/c1-30(2)17-18-9-8-12-21(15-18)28-25(19-10-6-5-7-11-19)24-22-14-13-20(27(33)31(3)4)16-23(22)29-26(24)32/h5-16,29,32H,17H2,1-4H3
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| Chemical Name |
3-[N-[3-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-N,N-dimethyl-1H-indole-6-carboxamide
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| Synonyms |
BIX 02189; BIX-02189; BIX02189
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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 |
| 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 | 2.2699 mL | 11.3497 mL | 22.6994 mL | |
| 5 mM | 0.4540 mL | 2.2699 mL | 4.5399 mL | |
| 10 mM | 0.2270 mL | 1.1350 mL | 2.2699 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.
Inhibition of ERK5 suppresses laminar flow-mediated Nrf2-dependent gene expression.J Biol Chem.2012 Nov 23;287(48):40722-31. |
ERK5 activation increases transcriptional activity of Nrf2.J Biol Chem.2012 Nov 23;287(48):40722-31. |
ERK5 is required for laminar flow-induced Nrf2 nuclear translocation.
Inhibition of ERK5 suppresses Nrf2 nuclear translocation in mouse aortain vivo. |
ERK5 binds to Nrf2 in a kinase activity-dependent manner.J Biol Chem.2012 Nov 23;287(48):40722-31. |
ERK5 activation protects against oxidative stress-induced cytotoxicity dependent on Nrf2.J Biol Chem.2012 Nov 23;287(48):40722-31. |
Depletion of KLF2 fails to inhibit laminar flow-induced Nrf2-dependent gene expression. |
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