BIX 02189


Catalog No. size PriceQuantity
M7121-2 2mg solid $87
M7121-10 10mg solid $365

Description

Cas:1265916-41-3

Product Information

BIX 02189 is a selective MEK5/ERK5 inhibitor with an IC50 of 59 nM. BIX02189 was reported to inhibit catalytic function of purified, MEK5 enzyme. BIX02189 blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. BIX02189 also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. BIX02189 may offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems.

 

Chemical Formula: C27H28N4O2

 

Exact Mass: 440.22123

Molecular Weight: 440.54

 

Elemental Analysis: C, 73.61; H, 6.41; N, 12.72; O, 7.26

 

Synonym:

 

BIX02189

BIX 02189

BIX-02189

 

Chemical Name: (Z)-3-(((3-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-N,N-dimethyl-2-oxoindoline-6-carboxamide

 

InChi Key: 

HOMJAAIVTDVQJA-IZHYLOQSSA-N

 

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/h5-16,28H,17H2,1-4H3,(H,29,32)/b25-24-

 

Smiles Code:

O=C(C1=CC(NC/2=O)=C(C=C1)C2=C(NC3=CC=CC(CN(C)C)=C3)/C4=CC=CC=C4)N(C)C

 

 

Technical Data:

 

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro

BIX02189 blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. BIX02189 inhibits ERK5 phosphorylation in a dose dependent manner. Fluvastatin reduces advanced glycation endproduct (AGE)-induced vascular smooth muscle cells (VSMCs) proliferation. To confirm this effect, VSMCs are treated with AGEs in the presence or absence of Fluvastatin and then subject to MTT assay. AGEs are found to dose-dependently induce cell proliferation, and this is significantly suppressed by Fluvastatin. In addition to MTT assay, the similar results are got with cell counting. This suppressive effect of Fluvastatin is prevented when VSMCs are pretreated with BIX02189. Whether ERK5 activation can reduce proliferation is also examined by using Ad-CA-MEK5α encoding a constitutively active mutant form of MEK5α (an upstream kinase of ERK5). AGE-induced proliferation determined by both MTT assay and cell counting is significantly diminished in the presence of Ad-CA-MEK5α, and Nrf2 depletion using siRNA restored AGE-induced proliferation.

 

In Vivo

Mice are treated with either 10 mg/kg of BIX02189 (in 25% DMSO) or vehicle control (same volume of 25% DMSO) by intraperitoneal injection. The nuclear localization of Nrf2 is inhibited in aortic endothelial cells from mice treated with BIX02189.

 

 

References

 

  1. Amano S, Chang YT, Fukui Y. ERK5 Activation Is Essential for Osteoclast Differentiation. PLoS One. 2015 Apr 17;10(4):e0125054. doi: 10.1371/journal.pone.0125054. eCollection 2015. PubMed PMID: 25885811; PubMed Central PMCID: PMC4401765.

 

  1. Geng X, Liu S, Chen Y. [Involvement of ERK5 and JNK in the BMP9-induced differentiation of C3H10T1/2 cells into cardiomyocyte-like cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014 Aug;30(8):829-32, 840. Chinese. PubMed PMID: 25108436.

 

  1. Lopez-Royuela N, Rathore MG, Allende-Vega N, Annicotte JS, Fajas L, Ramachandran B, Gulick T, Villalba M. Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells. Int J Biochem Cell Biol. 2014 Aug;53:253-61. doi: 10.1016/j.biocel.2014.05.026. Epub 2014 May 28. PubMed PMID: 24880091.

 

  1. Wang X, Pesakhov S, Weng A, Kafka M, Gocek E, Nguyen M, Harrison JS, Danilenko M, Studzinski GP. ERK 5/MAPK pathway has a major role in 1α,25-(OH)2 vitamin D3-induced terminal differentiation of myeloid leukemia cells. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:223-7. doi: 10.1016/j.jsbmb.2013.10.002. Epub 2013 Oct 26. Review. PubMed PMID: 24514755; PubMed Central PMCID: PMC4000286.

 

  1. Wang X, Pesakhov S, Harrison JS, Danilenko M, Studzinski GP. ERK5 pathway regulates transcription factors important for monocytic differentiation of human myeloid leukemia cells. J Cell Physiol. 2014 Jul;229(7):856-67. doi: 10.1002/jcp.24513. PubMed PMID: 24264602; PubMed Central PMCID: PMC4363988.

 

Products are for research use only. Not for human use.

 

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