WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206543
CAS#: 1207293-36-4
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.
MedKoo Cat#: 206543
Name: BI-847325
CAS#: 1207293-36-4
Chemical Formula: C29H28N4O2
Exact Mass: 464.2212
Molecular Weight: 464.569
Elemental Analysis: C, 74.98; H, 6.08; N, 12.06; O, 6.89
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
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 16.0 | 34.44 | |
| DMF:PBS (pH 7.2) (1:6) | 0.14 | 0.3 | |
| DMSO | 13.56 | 29.19 | |
| Ethanol | 0.65 | 1.4 |
The following data is based on the product molecular weight 464.569 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: | 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 vivo 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. |
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.
