BI-847325 | CAS#1207293-36-4 | MEK inhibitor

MedKoo Cat#: 206543 | Name: BI-847325

Description:

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

BI-847325 is an orally available dual inhibitor of mitogen-activated protein kinase kinase (MEK) and Aurora kinases, with potential antineoplastic activity. Upon oral administration, MEK/Aurora kinase inhibitor BI 847325 selectively binds to and inhibits the activity of MEK, which both prevents the activation of MEK-dependent effector proteins and inhibits growth factor-mediated cell signaling. BI 847325 also binds to and inhibits the activity of the Aurora kinases A, B and C which may disrupt the assembly of the mitotic spindle apparatus, prevent chromosome segregation, and inhibit both cellular division and proliferation in Aurora kinase-overexpressing tumor cells.

Chemical Structure

BI-847325

CAS#1207293-36-4

Theoretical Analysis

MedKoo Cat#: 206543

Name: BI-847325

CAS#: 1207293-36-4

Chemical Formula: C29H28N4O2

Exact Mass: 464.2212

Molecular Weight: 464.57

Elemental Analysis: C, 74.98; H, 6.08; N, 12.06; O, 6.89

Price and Availability

Size	Price	Availability
50mg	USD 650.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,350.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 4,950.00	2 Weeks
5g	USD 8,650.00	2 Weeks

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Synonym

BI-847325; BI 847325; BI847325.

IUPAC/Chemical Name

(Z)-3-(3-((4-((dimethylamino)methyl)phenylamino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide

InChi Key

FLBNLJLONKAPLR-DQSJHHFOSA-N

InChi Code

InChI=1S/C29H28N4O2/c1-4-30-26(34)17-13-20-12-16-24-25(18-20)32-29(35)27(24)28(22-8-6-5-7-9-22)31-23-14-10-21(11-15-23)19-33(2)3/h5-12,14-16,18,31H,4,19H2,1-3H3,(H,30,34)(H,32,35)/b28-27-

SMILES Code

O=C(NCC)C#CC1=CC(NC/2=O)=C(C=C1)C2=C(NC3=CC=C(CN(C)C)C=C3)/C4=CC=CC=C4

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

BI-847325 is an ATP competitive dual inhibitor of MEK and aurora kinases (AK) with IC50 values of 4 and 15 nM for human MEK2 and AK-C, respectively.

In vitro activity:

The effects of BI 847325 in a cellular environment were investigated in a BRAFV600E-mutant melanoma cell line (A375) and a KRASQ61K-mutant NSCLC cell line (Calu-6). Proliferation was inhibited in both cell lines with GI50 values of 7.5 and 60 nmol/L, respectively. Western blot analysis indicated that in A375 cells, BI 847325 potently reduced the concentration of phospho-ERK, an indicator of MAPK pathway activity (partial to complete inhibition at 10–30 nmol/L), whereas about 10-fold higher concentrations were required in Calu-6 cells (Fig. 2A). Reference: Mol Cancer Ther. 2016 Oct;15(10):2388-2398. https://mct.aacrjournals.org/content/15/10/2388.long

In vivo activity:

BI 847325 induced gradual regression of A375 tumors in a mouse xenograft model that was sustained for the entire 4-week treatment period (Fig. 5A). In the Calu-6 model, sustained tumor stasis was observed upon treatment with BI 847325. Treatment with BI 847325 resulted in a profound decrease of phospho-HH3–positive cells in both models, whereas reduction in phospho-ERK was observed only in BRAF-mutant A375 xenografts. Reference: Mol Cancer Ther. 2016 Oct;15(10):2388-2398. https://mct.aacrjournals.org/content/15/10/2388.long

	Solvent	mg/mL	mM
Solubility
	DMF	16.0	34.44
	DMF:PBS (pH 7.2) (1:6)	0.1	0.30
	DMSO	13.6	29.19
	Ethanol	0.7	1.40

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 464.57 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. Sini P, Gürtler U, Zahn SK, Baumann C, Rudolph D, Baumgartinger R, Strauss E, Haslinger C, Tontsch-Grunt U, Waizenegger IC, Solca F, Bader G, Zoephel A, Treu M, Reiser U, Garin-Chesa P, Boehmelt G, Kraut N, Quant J, Adolf GR. Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases. Mol Cancer Ther. 2016 Oct;15(10):2388-2398. doi: 10.1158/1535-7163.MCT-16-0066. Epub 2016 Aug 5. PMID: 27496137.

In vitro protocol:

In vivo protocol:

1: Schöffski P, Aftimos P, Dumez H, Deleporte A, De Block K, Costermans J, Billiet M, Meeus MA, Lee C, Schnell D, Goeldner RG, Awada A. A phase I study of two dosing schedules of oral BI 847325 in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jan;77(1):99-108. doi: 10.1007/s00280-015-2914-5. Epub 2015 Dec 9. PubMed PMID: 26650227. 2: Phadke MS, Sini P, Smalley KS. The Novel ATP-Competitive MEK/Aurora Kinase Inhibitor BI-847325 Overcomes Acquired BRAF Inhibitor Resistance through Suppression of Mcl-1 and MEK Expression. Mol Cancer Ther. 2015 Jun;14(6):1354-64. doi: 10.1158/1535-7163.MCT-14-0832. Epub 2015 Apr 14. PubMed PMID: 25873592; PubMed Central PMCID: PMC4458462.