MedKoo Cat#: 401150 Name: BIX 02189 CAS#: 1265916-41-3 (or 1094614-85-3) Chemical Formula: C27H28N4O2 Exact Mass: 440.22123 Molecular Weight: 440.53682 Elemental Analysis: C, 73.61; H, 6.41; N, 12.72; O, 7.26
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
Technical Data
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Certificate of Analysis: View CoA: current batch, Lot#TZC50520
QC Data: View QC data: current batch, Lot#TZC50520
Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)
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).
Harmonized System Code: 293490
Additional Information
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).
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.
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.
