TAE684 (NVP-TAE684)

製品コードS1108 バッチS110802

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₀H₄₀ClN₇O₃S

分子量

614.2

CAS No.

761439-42-3

Solubility (25°C)*

体外

DMSO

30 mg/mL (48.84 mM)

Ethanol

2 mg/mL (3.25 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	TAE684 (NVP-TAE684)は、強力かつ選択的なALK阻害剤であり、ALCL由来のALK依存性細胞株の増殖を阻止し、IC50値は2～10 nM、3 nMであり、InsRより100倍高いALK感受性を示した。TAE684 (NVP-TAE684)は細胞周期停止とapoptosisを誘導する。
in vitro	TAE684 (NVP-TAE684) does not exhibit significant cross-reactivity against other kinases. This compound potently inhibits the proliferation of Ba/F3 NPM-ALK cells with IC50 of 3 nM, without affecting the survival of Ba/F3 cells even at 1 μM. It also inhibits proliferation of NPM-ALK-expressing human ALCL cell lines including Karpas-299 and SU-DHL-1 with IC50 of 2–5 nM. Molecular modeling reveals that L258 may be one of the major kinase-selectivity determinants for this chemical. Its treatment results in a rapid and sustained inhibition of phosphorylation of NPM-ALK. The compound induces apoptosis and G1 phase arrest in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines. It markedly overcomes resistance in H3122 CR cells, harboring the fusion oncogene EML4-ALK, decreasing cell growth, suppressing ALK phosphorylation and inducing apoptosis. Neurite outgrowth induced by expression of the mALK R1279Q mutant could be completely inhibited by this compound at 30 nM.
in vivo	After 4 weeks of treatment with TAE684 (NVP-TAE684) at 3 and 10 mg/kg, there is a significant delay in lymphoma development and 100- to 1,000-fold reduction in luminescence signal, without any signs of compound- or disease-related toxicity in Karpas-299 lymphoma model. This compound treatment also induces disease regression in established Karpas-299 lymphomas and down-regulates CD30 expression. It also shows impressive antitumor activity against H3122 CR xenograft tumors. Furthermore, treatment with this chemical improves the rough eye phenotype of both ALK mutants, especially that seen with ALKR1275Q.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro Enzyme Assays.
キナーゼアッセイ	All in vitro enzyme assays are done at Upstate Biotechnology with the exception of InsR and IGF-1R. To determine the IC50 of TAE684 (NVP-TAE684) against InsR and IGF-1R a homogeneous time-resolved fluorescence assay is performed. ATP (10 mM) and 20 mg/ml biotinylated PolyEY (Glu, Tyr 4:1) are combined with 50 nL of serial dilutions of this compound (10-500 nM) and 4 ng of InsR enzyme in the presence of the kinase reaction buffer (20 mM Tris–Cl, pH 7.5/10 mM MgCl₂/3 mM MnCl₂/1 mM DTT/10 mM NaVO₄/0.1 mg/ml of BSA). Assays are incubated for 1 hour at ambient temperature. Reactions are terminated by adding 10 mL of the detection solution containing 50 mM EDTA, 500 mM KF, 0.5 mg/ml of BSA, 5 mg/mL Eu3+ cryptate-labeled anti-phosphotyrosine antibody Mab PT66-K, and 5 mg/mL Streptavidin-XLent. The reaction is incubated for half an hour, and fluorescence signals are read on Analyst GT.
細胞アッセイ	細胞株	Luciferase-expressing Karpas-299, SU-DHL-1, and Ba/F3 cells and transformed Ba/F3 stably expressing NPM-ALK, Bcr-Abl, or TEL-kinase fusion constructs.
	濃度	1 nM-10 μM
	反応時間	2–3 days
	実験の流れ	Cells are seeded in 384-well plates (2.5×10⁴ cells per well) and incubated with serial dilutions of TAE684 (NVP-TAE684) or DMSO for 2–3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. IC50 values are generated by using XLFit software.
動物実験	動物モデル	Karpas-299 xenografts are established in 4- to 6-week old female Fox Chase SCIDBeige mice.
	投薬量	1, 3, and 10 mg/kg
	投与方法	Once daily by oral gavage for 3 weeks

参考

https://pubmed.ncbi.nlm.nih.gov/17185414/
https://pubmed.ncbi.nlm.nih.gov/21502504/
https://pubmed.ncbi.nlm.nih.gov/21838707/

カスタマーフィードバック

: Data from [Cancer Res, 2011, 71, 4920-31]

: Data from [Neoplasia, 2011, 13, 704-15]

: Data from [Neoplasia, 2011, 13, 704-15]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Wnt Inhibition Safeguards Porcine Embryonic Stem Cells From the Acquisition of Extraembryonic Endoderm Cell Fates [ Adv Sci (Weinh), 2025, 12(17):e2416802]	PubMed: 40063421
Selective impact of ALK and MELK inhibition on ERα stability and cell proliferation in cell lines representing distinct molecular phenotypes of breast cancer [ Sci Rep, 2024, 14(1):8200]	PubMed: 38589728
LTK and ALK promote neuronal polarity and cortical migration by inhibiting IGF1R activity [ EMBO Rep, 2023, 24(7):e56937]	PubMed: 37291945
Development of the nonreceptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness [ J Biol Chem, 2023, 299(6):104825]	PubMed: 37196766
Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer [ Pharmacol Res Perspect, 2023, 11(1):e01047]	PubMed: 36583451
Selective Impact of ALK and MELK Inhibition on ERα Stability and Cell Proliferation in Cell Lines Representing Distinct Molecular Phenotypes of Breast Cancer [ bioRxiv, 2023, 10.1101/2023.12.19.572304]	PubMed: none
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9]	PubMed: 35868306
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304]	PubMed: 35704690
Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach [ EBioMedicine, 2022, 78:103963]	PubMed: 35339898
FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells [ Elife, 2022, 11e76183]	PubMed: 35550247

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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