BIX 02189
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Hodoodo CAT#: H401150

CAS#: 1265916-41-3

Description: 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 Structure

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BIX 02189
CAS# 1265916-41-3

Theoretical Analysis

Hodoodo Cat#: H401150
Name: BIX 02189
CAS#: 1265916-41-3
Chemical Formula: C27H28N4O2
Exact Mass: 440.22
Molecular Weight: 440.540
Elemental Analysis: C, 73.61; H, 6.41; N, 12.72; O, 7.26

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 Ready to ship
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Related CAS #: 1265916-41-3   1094614-85-3    

Synonym: BIX02189; BIX 02189; BIX-02189.

IUPAC/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

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

More Info: BIX02189 is a newly detected inhibitor of MEK5 and ERK5 and plays a significant role in detecting the specific effects of ERK5. Tyrosine hydroxylase enzyme is required for the synthesis of catecholamines and its levels are controlled by ERK5. BIX02189 helped to study the role of ERK5 in maintaining the levels of Tyrosine hydroxylase. This inhibitor opens the gateway to analyze the physiological effects of MEK5/ERK5 pathway.   ERK5 is a member of the MAPK family of proteins. Its activation is required the regular maintenance and growth of neuronal tissues. BIX 02189 inhibits the phosphorylation of ERK5. BIX 02189 has been effectively used to study the physiological role of ERK5. The molecular size of ERK5 is twice as big as ERK1/2 and the amino terminal of this protein is homologous to ERK1/2. However the carboxy terminus of this protein is unique as it has 2 proline rich regions and one NLS (source: http://www.zimbio.com).       

Biological target: BIX02189 is a MEK5 inhibitor with an IC50 of 1.5 nM and also inhibits ERK5 catalytic activity with an IC50 of 59 nM.
In vitro activity: Immunoblot analysis using protein lysates from NRK-Ctrl cells treated with increasing doses of BIX02189 (1.5–10 μM) demonstrated reduced phosphorylation of ERK5, but not ERK1/2, compared to vehicle (DMSO)-treated cells (Supplemental Figure 1). In the presence of two different doses of BIX02189 within the range used for the immunoblot, a dose-dependent reduction in cell number was calculated at both doses, but reached significance at the higher dose (10 μM; P < 0.05 at both time points) compared to the vehicle-treated NRK-Ctrl cells. Treatment of the NRK cells expressing AGS3 shRNA with BIX02189 resulted in poor viability of the cells that could not be maintained beyond 24 hours of incubation (data not shown). Reference: J Mol Signal. 2015; 10: 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831271/
In vivo activity: In order to figure out whether the activation of ERK5 in beta cells may be necessary for the augmentation of beta‐cell proliferation during pregnancy, this study injected a specific inhibitor of ERK5 activation, BIX02189, into the pregnant mice to suppress ERK5 signalling. At gestational day 15, mouse islets were isolated and examined for the levels of ERK5 and pERK5. The total ERK5 in islets from the pregnant mice that had received either BIX02189 or control saline did not alter (Figure 3A,B), while the phosphorylated ERK5 was significantly decreased in islets from the pregnant mice that had received BIX02189, compared with those from the pregnant mice that had received saline (Figure 3A,C). Thus, activation of ERK5 in beta cells in pregnant mice is suppressed by BIX02189 injections. Reference: Cell Prolif. 2018 Jun; 51(3): e12410. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528926/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 34.5 78.27
DMF 15.0 34.05
DMF:PBS (pH 7.2) (1:1) 0.5 1.13
Ethanol 10.0 22.70

Preparing Stock Solutions

The following data is based on the product molecular weight 440.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 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. PMID: 25885811; PMCID: PMC4401765. 2. Rasmussen SA, Kwon M, Pressly JD, Blumer JB, Regner KR, Park F. Activator of G-protein Signaling 3 Controls Renal Epithelial Cell Survival and ERK5 Activation. J Mol Signal. 2015 Nov 27;10:6. doi: 10.5334/1750-2187-10-5. PMID: 27096004; PMCID: PMC4831271. 3. Chen C, Wu S, Lin X, Wu D, Fischbach S, Xiao X. ERK5 plays an essential role in gestational beta-cell proliferation. Cell Prolif. 2018 Jun;51(3):e12410. doi: 10.1111/cpr.12410. Epub 2017 Nov 21. PMID: 29159830; PMCID: PMC6528926. 4. Nam DH, Han JH, Lim JH, Park KM, Woo CH. CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis. Mol Cells. 2017 Jul 31;40(7):457-465. doi: 10.14348/molcells.2017.2296. Epub 2017 Jul 6. PMID: 28681594; PMCID: PMC5547215.
In vitro protocol: 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. PMID: 25885811; PMCID: PMC4401765. 2. Rasmussen SA, Kwon M, Pressly JD, Blumer JB, Regner KR, Park F. Activator of G-protein Signaling 3 Controls Renal Epithelial Cell Survival and ERK5 Activation. J Mol Signal. 2015 Nov 27;10:6. doi: 10.5334/1750-2187-10-5. PMID: 27096004; PMCID: PMC4831271.
In vivo protocol: 1. Chen C, Wu S, Lin X, Wu D, Fischbach S, Xiao X. ERK5 plays an essential role in gestational beta-cell proliferation. Cell Prolif. 2018 Jun;51(3):e12410. doi: 10.1111/cpr.12410. Epub 2017 Nov 21. PMID: 29159830; PMCID: PMC6528926. 2. Nam DH, Han JH, Lim JH, Park KM, Woo CH. CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis. Mol Cells. 2017 Jul 31;40(7):457-465. doi: 10.14348/molcells.2017.2296. Epub 2017 Jul 6. PMID: 28681594; PMCID: PMC5547215.

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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.

2: 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.

3: 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.

4: 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.

5: 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.

6: Evans C, Cook SJ, Coleman MP, Gilley J. MEK inhibitor U0126 reverses protection of axons from Wallerian degeneration independently of MEK-ERK signaling. PLoS One. 2013 Oct 4;8(10):e76505. doi: 10.1371/journal.pone.0076505. eCollection 2013. PubMed PMID: 24124570; PubMed Central PMCID: PMC3790678.

7: Zhao LG, Chen SL, Teng YJ, An LP, Wang J, Ma JL, Xia YY. The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation. Connect Tissue Res. 2014 Apr;55(2):96-102. doi: 10.3109/03008207.2013.853755. Epub 2014 Jan 10. PubMed PMID: 24111522.

8: Kim S, Lim JH, Woo CH. ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation. Am J Pathol. 2013 Dec;183(6):1758-68. doi: 10.1016/j.ajpath.2013.08.014. Epub 2013 Oct 1. PubMed PMID: 24095924.

9: Obara Y. [Roles of ERK5 in neuronal cells]. Nihon Yakurigaku Zasshi. 2013 May;141(5):251-5. Review. Japanese. PubMed PMID: 23665555.

10: Kim M, Kim S, Lim JH, Lee C, Choi HC, Woo CH. Laminar flow activation of ERK5 protein in vascular endothelium leads to atheroprotective effect via NF-E2-related factor 2 (Nrf2) activation. J Biol Chem. 2012 Nov 23;287(48):40722-31. doi: 10.1074/jbc.M112.381509. Epub 2012 Oct 5. PubMed PMID: 23043106; PubMed Central PMCID: PMC3504785.