product name TAE226 (NVP-TAE226)
Description: TAE226 (also known as NVP-TAE226) is a potent and selective small molecule FAK inhibitor with IC50 of 5.5 nM and is modestly potent to Pyk2, ~10- to 100-fold less potent against InsR, IGF-1R, ALK, and c-Met. When tested with glioma cell lines U87, U87/EGFR, U87/EGFRvIII and U251 that expressed different level of FAK, TAE226 (NVP-TAE226) showed effective inhibition on the growth of the 4 cell lines in a dose dependent manner (1 and 10 μmol/L) and U87/EGFR, as well as U87/EGFRvIII, which had higher p-FAK expression than U87 were more sensitive to TAE226 (NVP-TAE226).
References: Mol Cancer Ther. 2007 Apr;6(4):1357-67; Invest New Drugs. 2010 Dec;28(6):825-33.
468.94
Formula
C23H25ClN6O3
CAS No.
761437-28-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 94 mg/mL (200.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
NVP-TAE226
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420144
| In Vitro |
In vitro activity: NVP-TAE226 (< 1 μM) inhibits extracellular matrix-induced autophosphorylation of FAK (Tyr397) in serum-starved U87 cells. NVP-TAE226 (< 1 μM) also inhibits IGF-I-induced phosphorylation of IGF-1R and activity of its downstream target genes such as MAPK and Akt in both U87 and U251 cells. NVP-TAE226 (<10 μM) retards tumor cell growth and attenuats G(2)-M cell cycle progression associated with a decrease in cyclin B1 and phosphorylated cdc2 (Tyr15) protein expression in both U87 and U251 cells. NVP-TAE226 (1 μM) inhibits tumor cell invasion by at least 50% compared with the control in an in vitro Matrigel invasion assay in glioma cell lines. NVP-TAE226 (1 μM) treatment of glioma cell lines containing wild-type p53 mainly exhibits G(2)-M arrest, whereas glioma cell lines bearing mutant p53 undergoes apoptosis, as evidence by detection of caspase-3/7 activation and poly(ADP-ribose) polymerase cleavage and by an Annexin V apoptosis assay. NVP-TAE226 (5 μM) inhibits phosphorylation of FAK in the human neuroblastoma cell line SK-N-AS. NVP-TAE226 (<10 μM) treatment of the human neuroblastoma cell line SK-N-AS leads to decrease in cellular viability, cell cycle arrest, and an increase in apoptosis. NVP-TAE226 (0.1 μM-10 μM) inhibits tube formation of HMEC1 cells. Kinase Assay: Cell Assay: 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 (U87 and U251 cell lines) are harvested at the indicated day after treatment, and viable cells are counted using the Vi-cell viability analyze. |
|---|---|
| In Vivo | NVP-TAE226 (75 mg/kg) significantly increases the survival rate of mice bearing intracranial glioma xenografts. NVP-TAE226 (100 mg/kg, oral) exerts significant decrease in microvessel density in a human colon cancer model in SCID mice. NVP-TAE226 (100 mg/kg, oral) efficiently inhibits MIA PaCa-2 human pancreatic tumor growth without body weight loss in vivo model. NVP-TAE226 inhibits 4T1 murine breast tumor growth and metastasis to the lung in a dose-dependent manner in vivo model, associated with inhibition of FAK autophosphorylation at Y397 and Akt phosphorylation at Serine473. |
| Animal model | Nude mice (male) bearing intracranial glioma xenografts |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose; 75 mg/kg; Oral gavage |
| References | Mol Cancer Ther. 2007 Apr;6(4):1357-67; Invest New Drugs. 2010 Dec;28(6):825-33. |
