BIX 02189
BIX 02189 is a selective inhibitor of MEK5 with IC50 value of 1.5 nM 1.
BIX 02189 belongs to the indolinone kinase inhibitor series. It selectively inhibited the catalytic activity of MEK5 but not other closely related kinases such as MEK1, MEK2, ERK2 and JNK2. BIX 02189 also inhibited ERK5 with IC50 value of 59 nM. In HeLa cells, treatment of BIX 02189 inhibited the phosphorylation of ERK5 but not ERK1/2. Besides that, BIX 02189 prevented the transcription of the downstream substrate MEF2C in HeLa and HEK293 cells. Moreover, in a three-dimensional lymphangiogenic sprouting assay, BIX 02189 resulted in an inhibition of lymphangiogenic sprouting with a minimal effective concentration of 1 μM 1,2.
References:
1. Tatake R J, O’Neill M M, Kennedy C A, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochemical and biophysical research communications, 2008, 377(1): 120-125.
2. Schulz M M P, Reisen F, Zgraggen S, et al. Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis. Proceedings of the National Academy of Sciences, 2012, 109(40): E2665-E2674.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 440.54 |
| Cas No. | 1094614-85-3 |
| Formula | C27H28N4O2 |
| Solubility | ≥22.05 mg/mL in DMSO; insoluble in H2O; ≥40.7 mg/mL in EtOH with ultrasonic |
| Chemical Name | (3Z)-3-[[3-[(dimethylamino)methyl]anilino]-phenylmethylidene]-N,N-dimethyl-2-oxo-1H-indole-6-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CN(C)CC1=CC(=CC=C1)NC(=C2C3=C(C=C(C=C3)C(=O)N(C)C)NC2=O)C4=CC=CC=C4 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment[1]: | |
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Cell lines |
HeLa cells |
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Preparation method |
The solubility of this compound in DMSO is > 22.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1.5 h, 10 μM |
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Applications |
BIX02189 inhibited MEK5 and ERK5 catalytic activity with IC50 values of 1.5 nM and 59 nM, respectively. BIX02189 inhibited ERK5 phosphorylation activated by sorbitol in a dose-dependent manner in HeLa cells. BIX02189 also inhibited luciferase gene expression induced by MEF2 in a dose dependent manner in HeLa and 293T cells. |
| Animal experiment [2]: | |
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Animal models |
Specific pathogen-free C57BL/6 mice |
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Dosage form |
Intraperitoneal injection, 10 mg/kg |
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Application |
BIX02189 significantly inhibited collagen accumulation and fibrogenic histological changes in the lung tissues of bleomycin-treated mice. BIX02189 also improved survival rate of mice after bleomycin inoculation. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Tatake R J, O’Neill M M, Kennedy C A, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway[J]. Biochemical and biophysical research communications, 2008, 377(1): 120-125. [2]. Kim S, Lim J H, Woo C H. ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation[J]. The American journal of pathology, 2013, 183(6): 1758-1768. | |
| Description | BIX02189 is a selective inhibitor of MEK5 with an IC50 value of 1.5 nM. | |||||
| Targets | MEK5 | ERK5 | TGFβR1 | |||
| IC50 | 1.5 nM | 59 nM | 580 nM | |||
Quality Control & MSDS
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Chemical structure
