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NVP-TAE 226

MCE China：NVP-TAE 226

Brand：MedChemExpress (MCE)

Cat. No.HY-13203

CAS：761437-28-9

Synonyms：TAE226

Purity：99.77%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year

Shipping：Room temperature in continental US; may vary elsewhere.

Description：NVP-TAE 226 (TAE226) is a potent and ATP-competitive dual FAK and IGF-1R inhibitor with IC50s of 5.5 nM and 140 nM, respectively. NVP-TAE 226 (TAE226) also effectively inhibits Pyk2 and insulin receptor (InsR) with IC50s of 3.5 nM and 44 nM, respectively.

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 IC50 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 (Tyr395). 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 G2-M cell cycle progression associated with a decrease in cyclin B1 and phosphorylated cdc2 (Tyr15) 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 G2-M arrest, whereas tumor cells bearing mutant p53 underwent apoptosis[1].

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 (Panimals)[1].

Animal Administration：Mice[1] Male nude mice used for this study are 6 to 8 weeks old. In DMEM/F12 serum-free media (5 μL), 5×105 of U87 cells and 1×106 of LN229 cells per mouse are implanted intracranially through a guide-screw system. Four days after injection of the tumor cells, mice are randomized into three groups for each cell line (n=6). Mice in group 1 are treated with 50 mg/kg NVP-TAE 226 in 200 μL of 0.5% methylcellulose, via an oral gavage. The mice in group 2 receive 75 mg/kg NVP-TAE 226 in 200 μL of 0.5% methylcellulose. The mice in group 3 the same vehicle used for administration of NVP-TAE 226 (control). Treatment frequency is once a day for 5 days and off for 2 days, for a duration of 4 weeks. Mice are monitored daily. Mice are euthanized when they are moribund, and the whole brain is extracted for rapid freezing in liquid nitrogen and storage at -70°C.

Cell Assay：Glioma cell cultures are harvested with 0.05% trypsin and seeded in triplicate at 2×104 in 24-well culture plates for 24 h before drug treatment. Culture medium is used for mock treatment. Cells are harvested at the indicated day after treatment, and viable cells are counted using the Vi-cell viability analyzer. The antiproliferative activity of NVP-TAE 226 (ranging from 0.25 to 1 μM) on cells growing in culture is determined using a tetrazolium-based colorimetric MTT assay[1].

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] Cellular Effect Cell Line Type Value Description References

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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.  [Content Brief]

[2]. Delimont D, et al. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS One. 2014 Jun 10;9(6):e99083.  [Content Brief]

[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.  [Content Brief]