BIX02188 | BIX-02188 | CAS#334949-59-6 | 1094614-84-2 | MEK5 inhibitor

MedKoo Cat#: 406775 | Name: BIX02188

Description:

WARNING: This product is for research use only, not for human or veterinary use.

BIX02188 is a potent inhibitor of MEK5 (IC50 = 4.3 nM) with reduced activity towards inhibition of ERK5 and TGFβR1 (IC50s = 810 and 1,800 nM, respectively). Inhibition of MEK5 by BIX02188 induces apoptosis in cells expressing the oncogenic mutant FLT3-ITD.

Chemical Structure

BIX02188

CAS#334949-59-6

Theoretical Analysis

MedKoo Cat#: 406775

Name: BIX02188

CAS#: 334949-59-6

Chemical Formula: C25H24N4O2

Exact Mass: 412.1899

Molecular Weight: 412.49

Elemental Analysis: C, 72.80; H, 5.86; N, 13.58; O, 7.76

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

334949-59-6 1094614-84-2

Synonym

BIX02188; BIX-02188; BIX 02188.

IUPAC/Chemical Name

(Z)-3-(((3-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-carboxamide

InChi Key

FSZPIAXLCCQFCM-FCQUAONHSA-N

InChi Code

InChI=1S/C25H24N4O2/c1-29(2)15-16-7-6-10-19(13-16)27-23(17-8-4-3-5-9-17)22-20-12-11-18(24(26)30)14-21(20)28-25(22)31/h3-14,27H,15H2,1-2H3,(H2,26,30)(H,28,31)/b23-22-

SMILES Code

CN(CC1=CC(N/C(C2=CC=CC=C2)=C3C(NC4=C\3C=CC(C(N)=O)=C4)=O)=CC=C1)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

Note: Two CAS# have been assigned for BIX02188 CAS#334949-59-6 CAS#1094614-84-2

Product Data

Product Data

Instruction

View handling instruction

Biological target:

BIX02188 is a potent MEK5-selective inhibitor with an IC50 of 4.3 nM. BIX02188 inhibits ERK5 catalytic activity, with an IC50 of 810 nM.

In vitro activity:

By use of the selective inhibitor of MEK5, BIX02188, this study has shown that activation of AKT downstream of FLT3 is partially dependent on ERK5. Furthermore, inhibition of MEK5/ERK5 induces apoptosis of both FLT3-ITD transfected Ba/F3 cells as well as the FLT3-ITD carrying leukemic cell lines MV4-11 and MOLM-13. Reference: Biochem Biophys Res Commun. 2011 Aug 26;412(2):307-12. https://pubmed.ncbi.nlm.nih.gov/21820407/

In vivo activity:

Spinal cord sections obtained from SCI rats revealed positive immunohistological staining for p-ERK5. Likewise, at 24 h after SCI or surgery, expression of p-ERK5 was investigated by Western blot. This study observed a significant increase of p-ERK5 levels in mice subjected to SCI. By contrast, BIX02188 treatment prevented SCI-induced p-ERK5 increases [Figure 1A–D]. Reference: Chin Med J (Engl). 2019 Nov 5; 132(21): 2601–2611. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6846248/

	Solvent	mg/mL	mM
Solubility
	DMSO	32.5	78.79
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.21
	DMF	20.0	48.49

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 412.49 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.

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. Razumovskaya E, Sun J, Rönnstrand L. Inhibition of MEK5 by BIX02188 induces apoptosis in cells expressing the oncogenic mutant FLT3-ITD. Biochem Biophys Res Commun. 2011 Aug 26;412(2):307-12. doi: 10.1016/j.bbrc.2011.07.089. Epub 2011 Jul 28. Erratum in: Biochem Biophys Res Commun. 2011 Nov 11;415(1):214. PMID: 21820407. 2. Liu CJ, Liu HY, Zhu ZQ, Zhang YY, Wang KF, Xia WW. Roles of extra-cellular signal-regulated protein kinase 5 signaling pathway in the development of spinal cord injury. Chin Med J (Engl). 2019 Nov 5;132(21):2601-2611. doi: 10.1097/CM9.0000000000000362. PMID: 31373906; PMCID: PMC6846248. 3. Wang CG, Song SY, Ding YL, Guo SQ, Liu X, Hao S, Li X, Chen N, Zhang Y, Zhang LC. Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats. Pain Physician. 2015 Nov;18(6):E1073-81. PMID: 26606020.

In vitro protocol:

In vivo protocol:

1. Liu CJ, Liu HY, Zhu ZQ, Zhang YY, Wang KF, Xia WW. Roles of extra-cellular signal-regulated protein kinase 5 signaling pathway in the development of spinal cord injury. Chin Med J (Engl). 2019 Nov 5;132(21):2601-2611. doi: 10.1097/CM9.0000000000000362. PMID: 31373906; PMCID: PMC6846248. 2. Wang CG, Song SY, Ding YL, Guo SQ, Liu X, Hao S, Li X, Chen N, Zhang Y, Zhang LC. Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats. Pain Physician. 2015 Nov;18(6):E1073-81. PMID: 26606020.

1: Wang CG, Song SY, Ding YL, Guo SQ, Liu X, Hao S, Li X, Chen N, Zhang Y, Zhang LC. Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats. Pain Physician. 2015 Nov;18(6):E1073-81. PubMed PMID: 26606020. 2: Chen Y, Li J, Zhu KY, Xiao S, Wang YQ, Wu GC, Wang J. [Electroacupuncture Intervention Enhances Splenic Natural Killer Cell Activity via Inhibiting Phosphorylation of ERK 5 in the Hypothalamus of Surgically Traumatized Rats]. Zhen Ci Yan Jiu. 2015 Jun;40(3):173-9. Chinese. PubMed PMID: 26237966. 3: Liang W, Fang D, Ye D, Zou L, Shen Y, Dai L, Xu J. Differential expression of extracellular-signal-regulated kinase 5 (ERK5) in normal and degenerated human nucleus pulposus tissues and cells. Biochem Biophys Res Commun. 2014 Jul 11;449(4):466-70. doi: 10.1016/j.bbrc.2014.05.042. Epub 2014 May 21. PubMed PMID: 24857985. 4: Badshah II, Baines DL, Dockrell ME. Erk5 is a mediator to TGFβ1-induced loss of phenotype and function in human podocytes. Front Pharmacol. 2014 Apr 21;5:71. doi: 10.3389/fphar.2014.00071. eCollection 2014. PubMed PMID: 24795631; PubMed Central PMCID: PMC4001011. 5: Obara Y. [Roles of ERK5 in neuronal cells]. Nihon Yakurigaku Zasshi. 2013 May;141(5):251-5. Review. Japanese. PubMed PMID: 23665555. 6: Wang CG, Ding YL, Zheng TF, Wei JQ, Liu H, Chen YF, Wang JY, Zhang LC. Extracellular signal-regulated kinase 5 in the cerebrospinal fluid-contacting nucleus contributes to morphine physical dependence in rats. J Mol Neurosci. 2013 May;50(1):215-20. doi: 10.1007/s12031-012-9915-1. Epub 2012 Nov 11. PubMed PMID: 23143893. 7: Koyama N, Hayashi T, Mizukoshi K, Matsumoto T, Gresik EW, Kashimata M. Extracellular regulated kinase5 is expressed in fetal mouse submandibular glands and is phosphorylated in response to epidermal growth factor and other ligands of the ErbB family of receptors. Dev Growth Differ. 2012 Dec;54(9):801-8. doi: 10.1111/dgd.12008. Epub 2012 Oct 19. PubMed PMID: 23078124. 8: Yu SJ, Grider JR, Gulick MA, Xia CM, Shen S, Qiao LY. Up-regulation of brain-derived neurotrophic factor is regulated by extracellular signal-regulated protein kinase 5 and by nerve growth factor retrograde signaling in colonic afferent neurons in colitis. Exp Neurol. 2012 Dec;238(2):209-17. doi: 10.1016/j.expneurol.2012.08.007. Epub 2012 Aug 19. PubMed PMID: 22921460; PubMed Central PMCID: PMC3498573. 9: Razumovskaya E, Sun J, Rönnstrand L. Inhibition of MEK5 by BIX02188 induces apoptosis in cells expressing the oncogenic mutant FLT3-ITD. Biochem Biophys Res Commun. 2011 Aug 26;412(2):307-12. doi: 10.1016/j.bbrc.2011.07.089. Epub 2011 Jul 28. Erratum in: Biochem Biophys Res Commun. 2011 Nov 11;415(1):214. PubMed PMID: 21820407. 10: Yang Q, Lee JD. Targeting the BMK1 MAP kinase pathway in cancer therapy. Clin Cancer Res. 2011 Jun 1;17(11):3527-32. doi: 10.1158/1078-0432.CCR-10-2504. Epub 2011 Mar 8. PubMed PMID: 21385929; PubMed Central PMCID: PMC3107913. 11: Wang CG, Lu XF, Wei JQ, Liu H, Zhang HX, Zhang LC, Cao JL. Activation of the spinal extracellular signal-regulated kinase 5 signaling pathway contributes to morphine physical dependence in rats. Neurosci Lett. 2011 Apr 20;494(1):38-43. doi: 10.1016/j.neulet.2011.02.049. Epub 2011 Feb 25. PubMed PMID: 21356274. 12: Obara Y, Nakahata N. The signaling pathway leading to extracellular signal-regulated kinase 5 (ERK5) activation via G-proteins and ERK5-dependent neurotrophic effects. Mol Pharmacol. 2010 Jan;77(1):10-6. doi: 10.1124/mol.109.060236. Epub 2009 Oct 26. Review. PubMed PMID: 19858097. 13: Obara Y, Yamauchi A, Takehara S, Nemoto W, Takahashi M, Stork PJ, Nakahata N. ERK5 activity is required for nerve growth factor-induced neurite outgrowth and stabilization of tyrosine hydroxylase in PC12 cells. J Biol Chem. 2009 Aug 28;284(35):23564-73. doi: 10.1074/jbc.M109.027821. Epub 2009 Jul 6. PubMed PMID: 19581298; PubMed Central PMCID: PMC2749131. 14: Tatake RJ, O'Neill MM, Kennedy CA, Wayne AL, Jakes S, Wu D, Kugler SZ Jr, Kashem MA, Kaplita P, Snow RJ. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5. doi: 10.1016/j.bbrc.2008.09.087. Epub 2008 Oct 1. PubMed PMID: 18834865. 15: Li L, Tatake RJ, Natarajan K, Taba Y, Garin G, Tai C, Leung E, Surapisitchat J, Yoshizumi M, Yan C, Abe J, Berk BC. Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells. Biochem Biophys Res Commun. 2008 May 23;370(1):159-63. doi: 10.1016/j.bbrc.2008.03.051. Epub 2008 Mar 19. PubMed PMID: 18358237; PubMed Central PMCID: PMC2435412.