TAE226

NVP-TAE226 is a potent FAK inhibitor with IC50 of 5.5 nM and modestly potent to Pyk2 (IC50=3.5 nM) ; 10- to 100-fold less potent against InsR, IGF-1R, ALK, and c-Met. (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. (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) .

761437-28-9

NVP-TAE226

>98% (HPLC)

DMSO: 94 mg/mL (200.45 mM)

O=C (NC) C1=CC=CC=C1NC2=NC (NC3=CC=C (N4CCOCC4) C=C3OC) =NC=C2Cl

C23H25ClN6O3

468.94

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.