[CAS NO. 761437-28-9] NVP-TAE226
PRODUCTS SPECIFICATIONS [761437-28-9]
DESCRIPTION [761437-28-9]
Overview
| MDL | MFCD12031516 |
|---|---|
| Molecular Weight | 468.94 |
| Molecular Formula | C23H25ClN6O3 |
| SMILES | O=C(C1=C(C=CC=C1)NC2=NC(NC3=C(C=C(C=C3)N4CCOCC4)OC)=NC=C2Cl)NC |
6 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 5.5 nM (FAK), 3.5 nM (Pyk2), 140 nM (IGF-IR), 40 nM (InsR), 0.16 μM (c-Met), 0.36 μM (KDR), 0.48 μM (Flt3) [1]
In Vitro
NVP-TAE 226 (TAE226), a potent ATP-competitive inhibitor of several tyrosine protein kinases, in particular FAK and IGF-IR kinases. In a cell-based kinase assays, FAK, IGF-IR kinase, and IR kinase are inhibited with an IC 50 range of 100 to 300 nM compared with the other kinases tested, which are >10-fold less sensitive. In culture, NVP-TAE 226 inhibits extracellular matrix-induced autophosphorylation of FAK (Tyr 395 ). NVP-TAE 226 also inhibits IGF-I-induced phosphorylation of IGF-IR and activity of its downstream target genes such as MAPK and Akt . NVP-TAE 226 retards tumor cell growth as assessed by a cell viability assay and attenuates G 2 -M cell cycle progression associated with a decrease in cyclin B1 and phosphorylated cdc2 (Tyr 15 ) protein expression. NVP-TAE 226 treatment inhibits tumor cell invasion by at least 50% compared with the control in an in vitro Matrigel invasion assay. Interestingly, TAE226 treatment of tumor cells containing wild-type p53 mainly exhibits G 2 -M arrest, whereas tumor cells bearing mutant p53 underwent apoptosis [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Treatment with NVP-TAE 226 (TAE226) at 50 or 75 mg/kg extends the median survival of U87 xenograft animals by 6 and 7 days, respectively (P=0.084 and P=0.042, respectively, compared with vehicle-treated animals). However, NVP-TAE 226 treatment of LN229-engrafted animals significantly prolongs their median survival by 19 days (P<0.004 for both dosages, compared with vehicle-treated animals) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 11.11 mg/mL ( 23.69 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1325 mL | 10.6623 mL | 21.3247 mL |
| 5 mM | 0.4265 mL | 2.1325 mL | 4.2649 mL |
| 10 mM | 0.2132 mL | 1.0662 mL | 2.1325 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: 1.11 mg/mL (2.37 mM); Clear solution; Need ultrasonic
References
- [1] Liu TJ, et al. Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther, 2007, 6(4), 1357-1367.
- [2] Delimont D, et al. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS One. 2014 Jun 10;9(6):e99083.
- [3] Lietha D, et al. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS One. 2008;3(11):e3800.