BIX02189 Chemical Properties

Boiling point:

653.4±55.0 °C(Predicted)

Density 

1.230±0.06 g/cm3(Predicted)

storage temp. 

2-8°C(protect from light)

solubility 

DMSO:34.48(Max Conc. mg/mL);78.27(Max Conc. mM)
DMF:15.0(Max Conc. mg/mL);34.05(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.13(Max Conc. mM)
Ethanol:10.0(Max Conc. mg/mL);22.7(Max Conc. mM)

form 

A crystalline solid

pka

11.61±0.20(Predicted)

color 

White to yellow

InChI

1S/C27H28N4O2/c1-30(2)17-18-9-8-12-21(15-18)28-25(19-10-6-5-7-11-19)24-22-14-13-20(27(33)31(3)4)16-23(22)29-26(24)32/h5-16,28H,17H2,1-4H3,(H,29,32)/b25-24-

InChIKey

HOMJAAIVTDVQJA-IZHYLOQSSA-N

SMILES

CN(C)CC1=CC=CC(N/C(C2=CC=CC=C2)=C(C3=CC=C(C(N(C)C)=O)C=C3N4)\C4=O)=C1

Safety Information

WGK Germany 

WGK 3

HS Code 

2933790090

Storage Class

11 - Combustible Solids

BIX02189 Usage And Synthesis

Uses

BIX 02189 inhibits TGF-b1-induced lung cancer cell metastasis by directly targeting TGF-b type I receptor.

Definition

ChEBI: 3-[[3-[(dimethylamino)methyl]anilino]-phenylmethylidene]-N,N-dimethyl-2-oxo-1H-indole-6-carboxamide is an indolecarboxamide.

Biological Activity

BIX02189 is an ATP site-targeting, potent and selective MEK5 inhibitor (IC50 =1.5 nM, [ATP] = 750 nM) with much reduced or no potency against 79 other kinases (CSF1R (FMS)/ERK5/Lck/Jak3/TGFβR1/RPS6KA6 (RSK4) IC50 = 46/59/250/440/580/990 nM, MEK1/MEK2/ERK2/JNK2/EGFR/STK16 IC50 >6.2 μM). BIX02189 blocks cellular ERK5, but not ERK1/2 or p38, phosphorylation induction (IC50 <1 μM in sorbitol-stimulated HeLa), as well as downstream MEF2C transcriptional activation (IC50 = 0.53/0.26 μM, MEK5/ERK5/MEF2C HeLa/HEK293 reporter cells). BIX02189 in vivo efficacies are demonstrated in murine models of atherosclerosis, cancer, and diabetes (10-20 mg/kg i.p.).

Enzyme inhibitor

This selective MEK/ERK pathway inhibitor (FW = 440.54 g/mol; CAS 1265916-41-3; Solubility: 100 mM in DMSO; 100 mM for monohydrochloride salt), also named (3Z)-3-[[[3-[(dimethylamino) methyl]phenyl]amino]phenylmethylene]-2,3-dihydro-N,N-dimethyl-2-oxo- 1H-indole-6-carboxamide, targets Mitogen/Extracellular signal-regulated Kinase-5, or MEK5 (IC50 = 1.5 nM), and Extracellular-signal-Regulated Kinase, or ERK5 (IC50 = 59 nM), showing far weaker effects on MEK1 (IC50 = 6200 nM), MEK2 (IC50 = >6200 nM), ERK1 (IC50 >6200 nM), JNK2 (IC50 >6200 nM), TGFβR1 (IC50 = 580 nM), EGFR (IC50 >6300 nM), and STK16 (IC50 >6300 nM). Pharmacology: ERK5 is an atypical MAPK that is activated in the heart by pressure overload. ERK5 regulates cardiac hypertrophy and hypertrophy-induced apoptosis, and silencing ERK5 expression or inhibiting its kinase activity with BIX02189 reduces Myocyte Enhancer Factor-2 (MEF2) transcriptional activity and blunted hypertrophic responses in neonatal rat cardiomyocytes, or NRCMs. By applying BIX02189 to NRCMs, ERK5 phosphorylation is blocked without affecting other MAP kinases. BIX02189 induces apoptosis in acute myeloid leukemia tumor cells without affecting T cells from healthy donors

storage

Store at -20°C