BI-847325 (BI847325) is a novel, potent, orally bioavailable, and selective dual inhibitor of MEK (mitogen-activated protein kinase kinase) and Aurora kinase with potential antitumor activity. It inhibits Aurora B, human Aurora A, Aurora C, MEK1 and MEK2 with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM, respectively. BI 847325 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.

Physicochemical Properties

Molecular Formula	C29H28N4O2
Molecular Weight	464.56
Exact Mass	464.221
Elemental Analysis	C, 74.98; H, 6.08; N, 12.06; O, 6.89
CAS #	1207293-36-4
Related CAS #	1207293-36-4
PubChem CID	135567102
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Index of Refraction	1.673
LogP	4.36
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	798
Defined Atom Stereocenter Count	0
SMILES	O([H])C1=C(/C(/C2C([H])=C([H])C([H])=C([H])C=2[H])=N/C2C([H])=C([H])C(=C([H])C=2[H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])C2C([H])=C([H])C(C#CC(N([H])C([H])([H])C([H])([H])[H])=O)=C([H])C=2N1[H]
InChi Key	OCUQMWSIGPQEMX-UHFFFAOYSA-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/h5-12,14-16,18,32,35H,4,19H2,1-3H3,(H,30,34)
Chemical Name	3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide
Synonyms	BI 847325; BI847325;BI-847325;(Z)-3-(3-((4-((dimethylamino)methyl)phenylamino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	BI 847325 prevents X from acting. It also inhibits human AK-A and AK-C, with IC50 values of 25 and 15 nM, respectively. laevis AK-B. Additionally, human MEK1 and MEK2 are inhibited by BI 847325, with IC50 values of 25 and 4 nM, respectively. BI 847325 LCK, MAP3K8, FGFR1, AMPK, CAMK1D, and TBK1 at 1000 nM; only LCK (5 nM) and MAP3K8 (93 nM) had IC50 values less than 100 nM. A375 and Calu-6 cell lines are inhibited by BI 847325, with GI50 values of 7.5 nM and 60 nM, respectively[1].
ln Vivo	Oral administration of BI 847325 at a dose of 10 mg/kg per day proved effective in BRAF and KRAS mutant xenograft tumor models. When given once a week at a dose of 70 mg/kg, BI 847325 suppresses AK and MEK in cancers with KRAS mutations [1].
Animal Protocol	Dissolved in 2-hydroxyethyl cellulose, polysorbate 80 with pH adjusted to 2.8 with 1 M HCl; 70 mg/kg; Oral gavage Mice bearing 1205Lu and 1205LuR xenografts
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO: 19 mg/mL (40.9 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2-hydroxyethyl cellulose, polysorbate 80 with pH adjusted to 2.8 with 1 M HCl:30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1526 mL	10.7629 mL	21.5257 mL
	5 mM	0.4305 mL	2.1526 mL	4.3051 mL
	10 mM	0.2153 mL	1.0763 mL	2.1526 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.