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Purity: ≥98%
TAE684 (also called NVP-TAE684; TAE-684) is a novel, highly potent and selective small-molecule inhibitor of the ALK (anaplastic lymphoma kinase) tyrosine kinase with potential anticancer activity. In a cell-free assay, it inhibits ALK with an IC50 of 3 nM. TAE 684 inhibits ALK with a sensitivity that is 100 times higher than InsR. With IC50 values between 2 and 10 nM, it exhibits strong anti-proliferative activity against ALK-dependent and ALCL-derived cell lines in vitro.
| Targets |
ALK (IC50 = 2-10 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
As a stock solution, 10 mM of GSK1904529A is dissolved in DMSO. The IC50 is determined using proteins tagged with glutathione S-transferase that are expressed by bacteria and encode the intracellular domain of IGF-1R (amino acids 957–1367) and IR (amino acids 979–1382). In order to activate kinases, the enzyme must be preincubated in 50 mM HEPES (pH 7.5), 10 mM MgCl2, 0.1 mg/mL bovine serum albumin, and 2 mM ATP at a final concentration of 2.7 μM. The assay plates are filled with 100 nL/well of diluted GSK1904529A, which has been diluted in DMSO. Kinase reactions that were present (in 10 μL) 0.5 nM activated enzyme, 500 nM substrate peptide (biotin-aminohexylAEEEEYMMMMAKKKK-NH2; QPC), 3 mM DTT, 0.1 mg/mL bovine serum albumin, 1 mM CHAPS, 10 mM MgCl2, and 10 μM ATP. After one hour at room temperature, reactions are terminated using 33 μM EDTA. Using 1 nM europium-conjugated phosphotyrosine antibodies and 7 nM streptavidin Surelight allophycocyanin, time-resolved fluorescence resonance energy transfer is used to measure phosphorylation of peptides. A multilabel reader is used to read plates.
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| Cell Assay |
In 384-well plates, cells are seeded with 2.5×104 cells per well, and they are then incubated for two to three days with TAE684 or DMSO serial dilutions. The Bright-Glo Luciferase Assay System is used to measure luciferase expression, which is a proxy for cell proliferation and survival. To generate IC50 values, use the XLFit software.
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| Animal Protocol |
In order to conduct in vivo compound efficacy studies, female Fox Chase SCIDBeige mice are injected with 1×106 Karpas-299-, Ba/F3 NPM-ALK-, or BCR-ABL-expressing cells via the tail vein 72 hours later. TAE684 resuspended in 10% 1-methyl-2-pyrrolidinone/90% PEG 300 solution is given to mice (n = 10 per group) at 1, 3, and 10 mg/kg once daily for three weeks, or the vehicle solution is given at the same dosing schedule. Bioluminescence imaging is used once a week to track the progression of the disease and the effectiveness of the compound. The disease is confirmed to be widespread by bioluminescence imaging on day 12, at which point dosing is started in order to assess the effectiveness of TAE684 on established disease. For three days, mice with established lymphomas are given either vehicle solution or TAE684 (10 mg/kg) in order to analyze the downstream molecular effects in vivo. Upon completion of therapy, lymph nodes are removed from the mice and subjected to immunoblotting and histological examination.
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| References |
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| Molecular Formula |
C30H40CLN7O3S
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| Molecular Weight |
614.2
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| Exact Mass |
613.26
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| Elemental Analysis |
C, 58.66; H, 6.56; Cl, 5.77; N, 15.96; O, 7.81; S, 5.22
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| CAS # |
761439-42-3
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| Related CAS # |
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| Appearance |
Pale yellow solid powder
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| SMILES |
CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
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| InChi Key |
QQWUGDVOUVUTOY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H40ClN7O3S/c1-21(2)42(39,40)28-8-6-5-7-26(28)33-29-24(31)20-32-30(35-29)34-25-10-9-23(19-27(25)41-4)37-13-11-22(12-14-37)38-17-15-36(3)16-18-38/h5-10,19-22H,11-18H2,1-4H3,(H2,32,33,34,35)
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| Chemical Name |
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
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| Synonyms |
NVP-TAE684; TAE 684; TAE684; NVP-TAE 684; NVP-TAE-684; TAE-684
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| HS Tariff Code |
2934.99.9001
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6281 mL | 8.1407 mL | 16.2813 mL | |
| 5 mM | 0.3256 mL | 1.6281 mL | 3.2563 mL | |
| 10 mM | 0.1628 mL | 0.8141 mL | 1.6281 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.
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