Catalog Number
ACM1207293364-1
Description
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.
Synonyms
BI-847325; BI 847325; BI847325
IUPAC Name
(Z)-3-(3-((4-((dimethylamino)methyl)phenylamino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide
Molecular Formula
C29H28N4O2
Canonical SMILES
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
InChI
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-
InChI Key
FLBNLJLONKAPLR-DQSJHHFOSA-N
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Storage
Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
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.
Drug Formulation
This drug may be formulated in DMSO
Elemental Analysis
C, 74.98; H, 6.08; N, 12.06; O, 6.89
HS Tariff Code
2934.99.9001
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
Shipping
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.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).
Download
