| Identification | Back Directory | [Name]
BIX02189 | [CAS]
1265916-41-3 | [Synonyms]
BIX02189 (BIX 02189)
(Z)-3-((3-((Dimethylamino)methyl)phenylamino)(phenyl)methylene)-N,N-dimethyl-2-oxoindoline-6-c
(3Z)-3-[[[3-[(Dimethylamino)methyl]phenyl]amino]phenylmethylene]-2,3-dihydro-N,N-dimethyl-2-oxo-1H-indole-6-carboxamide
1H-Indole-6-carboxamide, 3-[[[3-[(dimethylamino)methyl]phenyl]amino]phenylmethylene]-2,3-dihydro-N,N-dimethyl-2-oxo-, (3Z)- | [Molecular Formula]
C27H28N4O2 | [MDL Number]
MFCD18074528 | [MOL File]
1265916-41-3.mol | [Molecular Weight]
440.54 |
| Chemical Properties | Back Directory | [Boiling point ]
653.4±55.0 °C(Predicted) | [density ]
1.230±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [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 |
| Hazard Information | Back Directory | [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-targetingpotent 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 nMMEK1/MEK2/ERK2/JNK2/EGFR/STK16 IC50 >6.2 μM). BIX02189 blocks cellular ERK5but not ERK1/2 or p38phosphorylation induction (IC50 <1 μM in sorbitol-stimulated HeLa)as well as downstream MEF2C transcriptional activation (IC50 = 0.53/0.26 μMMEK5/ERK5/MEF2C HeLa/HEK293 reporter cells). BIX02189 in vivo efficacies are demonstrated in murine models of atherosclerosiscancerand 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 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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