5mg TAE684 （NVP-TAE684）
| 參考價 | ￥ 1308 |
| 訂貨量 | ≥1 |
- 公司名稱 上海高創(chuàng)化學(xué)科技有限公司
- 品牌 Selleck
- 型號 5mg
- 產(chǎn)地 美國
- 廠商性質(zhì) 代理商
- 更新時間 2017/11/20 13:34:06
- 訪問次數(shù) 571
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| 供貨周期 | 現(xiàn)貨 | 規(guī)格 | 5mg |
|---|---|---|---|
| 貨號 | S1108 | 主要用途 | 科研 |
TAE684 (NVP-TAE684)
化學(xué)數(shù)據(jù)
| 分子量 | 614.2 | 穩(wěn)定性 | 3年 -20°C粉狀 |
|---|---|---|---|
| 化學(xué)式 | C30H40ClN7O3S | -- -- -- | |
| CAS號 | 761439-42-3 | 別名 | N/A |
| Solubility (25°C) * | 體外 | DMSO | 3 mg/mL (4.88 mM) |
| Water | Insoluble | ||
| Ethanol | Insoluble | ||
| 體內(nèi) | 30% PEG400+0.5% Tween80+5% propylene glycol, pH 4 | 10 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. | |||
| 化學(xué)名 | 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine | ||
制備儲備液
| 濃度溶劑體積(DMSO)質(zhì)量 | 1 mg | 5 mg | 10 mg |
| 1 mM | 1.6281 mL | 8.1407 mL | 16.2813 mL |
| 5 mM | - | - | - |
| 10 mM | - | - | - |
| 50 mM | - | - | - |
生物活性
| 產(chǎn)品描述 | TAE684 (NVP-TAE684)是一種有效的,，選擇性ALK抑制劑，在無細胞試驗中IC50為3 nM,，作用于ALK比作用于InsR選擇性高100倍,。 | |||||
|---|---|---|---|---|---|---|
| 靶點 |
| |||||
| 體外研究 | NVP-TAE684選擇性有效抑制ALK激酶，作用于其他激酶則沒有明顯的交叉反應(yīng),。NVP-TAE684 有效抑制Ba/F3 NPM-ALK 細胞增殖,，IC50 為3 nM, 1 μM NVP-TAE684對Ba/F3 細胞存活沒有效果。NVP-TAE684 也抑制表達NPM-ALK人類ALCL細胞系的增殖,，包括Karpas-299和SU-DHL-1,，IC50為2-5 nM。分子模型顯示L258 可能為NVP-TAE684的主要激酶選擇性影響因素之一,。用NVP-TAE684處理,，快速且持久地抑制NPM-ALK的磷酸化作用。NVP-TAE684 作用于表達NPM-ALK的 Ba/F3 細胞和ALCL病患細胞系,，誘導(dǎo)細胞凋亡,，且使細胞周期停在G1期。[1] NVP-TAE684 作用于H3122 CR細胞,，顯著克服細胞抗Crizotinib的特性, 含有融合致癌基因EML4-ALK, 降低細胞生長,，抑制ALK磷酸化作用和誘導(dǎo)細胞凋亡。[2] 30 nM NVP-TAE684可抑制mALK R1279Q 突變表達誘導(dǎo)的神經(jīng)突增生。[3] | |||||
| 體內(nèi)研究 | 3和10 mg/kg NVP-TAE684處理4周后,明顯減慢淋巴癌生長轉(zhuǎn)移,，作用于Karpas-299淋巴癌模型沒有毒性。用NVP-TAE684處理Karpas-299 淋巴癌也誘導(dǎo)疾病衰退和下調(diào)CD30表達,。[1] NVP-TAE684 作用于H3122 CR移植瘤顯示出明顯的抗癌活性,。[2]用NVP-TAE684處理也提升ALK突變的表現(xiàn)型,尤其是ALKR1275Q, 然而Crizotinib 對表現(xiàn)型沒有影響。[3] | |||||
| 臨床實驗 | ||||||
| 特征 | NVP-TAE684 作為治療難*和復(fù)發(fā)的ALK陽性淋巴癌的一種策略,，但是還沒進行臨床實驗,。 | |||||
*的實驗操作 (此*來自于公開的文獻所以Selleck并不保證其有效性)
激酶實驗：[1]
| 體外酶實驗 | 使用同質(zhì)時間分辨熒光法測定NVP-TAE684作用于InsR和IGF1R的IC50 值。ATP (10 mM)和20 mg/ml 生物素PolyEY (Glu, Tyr 4:1),，與50 nL NVP-TAE684連續(xù)稀釋液 (10-500 nM) ,，和4 ng InsR 酶，和激酶反應(yīng)buffer (包括20 mM Tris×HCl, pH 為7.5 /10 mM MgCl2/3 mM MnCl2/1 mM DTT/10 mM NaVO4/0.1 mg/ml of BSA)混合,。在室溫下溫育1小時,。加入10 mL檢測液終止反應(yīng)，檢測液含50 mM EDTA, 500 mM KF, 0.5 mg/ml of BSA, 5 mg/ml Eu3+ 穴狀化合物標記的磷酸酪氨酸抗體PT66-K,及5 mg/ml 鏈霉親和素-XLent,。反應(yīng)進行半小時,，在Analyst GT上讀取熒光信號。 |
|---|
細胞實驗：[1]
| 細胞系 | 表達Luciferase的Karpas-299, SU-DHL-1,和Ba/F3 細胞,，及穩(wěn)定表達Ba/F3轉(zhuǎn)變的 NPM-ALK, BCR-ABL,或激酶融合構(gòu)成,。 |
|---|---|
| 濃度 | 1 nM-10 μM |
| 處理時間 | 2到3天 |
| 方法 | 細胞按每孔2.5×104個接種在384孔板上，和NVP-TAE684的連續(xù)稀釋液或DMSO溫育2到3天,。使用Luciferase表達系統(tǒng)測定細胞增殖和存活,，然后用Bright-Glo Luciferase 實驗系統(tǒng)測評。使用XLFit 軟件測定IC50值,。 |
動物實驗：[1]
| 動物模型 | 4到6周大的攜帶Karpas-299移植瘤的雌性Fox Chase SCIDBeige 鼠 |
|---|---|
| 配制 | 再懸浮在10% 1-甲基-2-吡咯烷酮/90%聚乙烯乙二醇300溶液中 |
| 劑量 | 1, 3, 和 10 mg/kg |
| 給藥處理 | 每天口服飼喂,，持續(xù)3周。 |
參考
- [1] Galkin AV, et al. Proc Natl Acad Sci U S A, 2007, 104(1), 270-275.
- [2] Katayama R, et al. Proc Natl Acad Sci U S A, 2011, 108(18), 7535-7540.
- [3] Sch?nherr C, et al, Biochem J, 2011, 440(3), 405-413.
客戶使用selleck產(chǎn)品的實驗數(shù)據(jù)
數(shù)據(jù)來源于[Cancer Res , 2011, 71, 4920-31]
(A) H3122 xenografts harboring the EML4-ALK translocation were treated with control vehicle or the ALK inhibitor, TAE-684, for 2 days; the tumors were excised and lysates were prepared. The TIMM results for the control and treated animals are shown. (B) H3122 cells were treated in the presence or absence of TAE-684 (100 nM) for 6 hours in the presence or absence of the indicated ligands [EGF (50 ng/mL), IGF1 (50 ng/mL), and HGF (50 ng/mL)]. Extracts were probed with the indicated antibodies.
數(shù)據(jù)來源于[Neoplasia, 2011, 13, 704-15]
Therapeutic effects of ALK inhibitor TAE684 on H694R- and E1384K-mediated tumorigenesis of H1299 transfectants. (B) Dosage effects of TAE684 on phospho-Y1604 ALK expression of wild-type, H694R, and E1384K transfectants by Western blot analysis (top panel). Quantitative results of phospho-Y1604 ALK intensity are also (bottom panel).
TAE684 (NVP-TAE684)在18個文獻中得到引用
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. [Wilson TR, et al. Nature, 2012, 487(7408):505-9]
PubMed: 22763448MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling. [Huang S, et al. Cell, 2012, 151(5):937-50]
PubMed: 23178117A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer [Wilson FH, et al. Cancer Cell, 2015, 27(3):397-408]
PubMed: 25759024SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer. [Papadakis AI, et al. Cell Res, 2015, 10.1038/cr.2015.16]
PubMed: 25656847Using tandem mass spectrometry in targeted mode to identify activators of class IA PI3K in cancer. [Yang X, et al. Cancer Res, 2011, 71(18):5965-75]
PubMed: 21775521Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. [Davies KD, et al. Clin Cancer Res, 2012, 18(17):4570-9]
PubMed: 22919003Upregulation of MAPK negative feedback regulators and RET in mutant ALK neuroblastoma: implications for targeted treatment. [Lambertz I, et al. Clin Cancer Res, 2015, 10.1158/1078-0432.CCR-14-2024]
PubMed: 25805801Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non–Small Cell Lung Cancer [Song A, et al. Clin Cancer Res, 2015, 21(10):2379-87]
PubMed: 25688157Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells. [Yamada T, et al. Clin Cancer Res, 2013, 18(13):3592-602]
PubMed: 22553343Lobatin b inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation. [Kiss I, et al. Cancer Lett, 2015, 356(2 Pt B):994-1006]
PubMed: 25444930Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation. [Hyeong Ryul Kim, et al. Mol Oncol, 2013, 7(6):1093-102]
PubMed: 23993685Resistance to targeted cancer drugs through hepatocyte growth factor signaling. [Heynen GJ, et al. Cell Cycle, 2014, 13(24):3808-17]
Interferon-γ induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages. [Kuss M, et al. J Neurochem, 2014, 129(6):980-7]
PubMed: 24479685Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. [Wang YW, et al. Neoplasia, 2011, 13(8):704-15]
PubMed: 21847362Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells. [Grygielewicz P, et al. Gastric Cancer, 2014, 10.1007/s10120-014-0444-1]
PubMed: 25407459Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. [Duong HQ, et al. Int J Oncol, 2013, 44(3):959-69]
PubMed: 24366069Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area. [Dutton JW 3rd, et al. Addict Biol, 2017, 22(3):665-678]
PubMed: 26752591Epithelial-mesenchymal transition confers resistance to FGFR inhibitors in gastric cancer cell line [Paulina Grygielewicz, et al. CELON PHARMA, 2013, 3]
如果需要*保存,，請于零下二十度低溫保存,。
禁止用于人體及治療！
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TAE684 (NVP-TAE684)
TAE684 (NVP-TAE684)
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