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Purity: ≥98%
TAE226 (also known as NVP-TAE226; TAE-226) is a novel, potent, selective and ATP competitive small molecule FAK (focal adhesion kinase) inhibitor with potential antineoplastic activity. It inhibits FAK with IC50 of 5.5 nM, shows modest potency against other kinases such as Pyk2, InsR, IGF-1R, ALK, and c-Met. TAE 226 demonstrate significant in vivo antitumor efficacy in Nude mice (male) bearing intracranial glioma xenografts. 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).
| ln Vitro |
Strong ATP competitive inhibitor NVP-TAE 226 (TAE226) inhibits several tyrosine protein kinases, particularly FAK and IGF-IR kinases. FAK, IGF-IR kinase, and IR kinase were inhibited in a cell-based kinase experiment with IC50s ranging from 100 to 300 nM. This was less sensitive than the other kinases examined, all of which had IC50s that were ten times higher. NVP-TAE 226 prevents FAK from becoming autophosphorylated in culture due to extracellular matrix (Tyr395). Additionally, IGF-I-induced phosphorylation of IGF-IR and the activity of its downstream target genes (including Akt and MAPK) are inhibited by NVP-TAE 226. NVP-TAE 226 attenuates G2-M cell cycle progression associated with decreased cyclin B1 and phosphorylated cdc2 (Tyr15) protein expression, and slows tumor cell development (measured by cell viability assay). Tumor cell invasion in the in vitro Matrigel invasion experiment was at least 50% reduced by NVP-TAE 226 treatment in comparison to the control. It's interesting to note that tumor cells with wild-type p53 exhibit primarily G2-M arrest upon TAE226 treatment, but tumor cells with mutant p53 experience apoptosis [1].
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| ln Vivo |
The median survival of U87 tumor xenograft rats was extended by 6 and 7 days, respectively, upon treatment with 50 or 75 mg/kg NVP-TAE 226 (TAE226) (P=0.084 and 7 days, respectively, in comparison to animals treated with a control group). P is equal to 0.042). On the other hand, the treatment of LN229 tumor xenograft animals with NVP-TAE 226 markedly increased their median survival time by 19 days (P<0.004 for both doses when compared to animals treated with vehicle) [1].
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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.
[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 |
| Molecular Formula |
C23H25CLN6O3
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| Molecular Weight |
468.94
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| CAS # |
761437-28-9
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| Related CAS # |
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| SMILES |
O=C(NC)C1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCOCC4)C=C3OC)=NC=C2Cl
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| InChi Key |
UYJNQQDJUOUFQJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25ClN6O3/c1-25-22(31)16-5-3-4-6-18(16)27-21-17(24)14-26-23(29-21)28-19-8-7-15(13-20(19)32-2)30-9-11-33-12-10-30/h3-8,13-14H,9-12H2,1-2H3,(H,25,31)(H2,26,27,28,29)
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| Chemical Name |
2-((5-chloro-2-((2-methoxy-4-morpholinophenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide
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| Synonyms |
TAE-226, TAE226, TAE 226, NVP-TAE226, NVPTAE226, NVP TAE226,
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.11 mg/mL (2.37 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1.11 mg/mL (2.37 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 0.5% methylcellulose:30 mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
TAE226 treatment inhibits FAK and IGF-IR signaling pathways.Mol Cancer Ther.2007 Apr;6(4):1357-67. |
TAE226 treatment induces apoptosis in glioma cells containing mutant p53.Mol Cancer Ther.2007 Apr;6(4):1357-67. |
TAE226 treatment prolongs the survival of glioma xenograft animals.Mol Cancer Ther.2007 Apr;6(4):1357-67. |
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