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TAK-659 hydrochloride

产品编号 T4209 CAS 1952251-28-3

别名: TAK-659

TAK-659 hydrochloride (TAK-659) 是可逆的、高效的、选择性的、口服有效的 SYK/FLT3 双抑制剂，对 SYK 和 FLT3 作用的IC50值分别为 3.2 nM、4.6 nM。它能诱导肿瘤细胞死亡，却不作用于非肿瘤细胞，对慢性淋巴细胞白血病具有潜在的研究价值。

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TAK-659 hydrochloride Chemical Structure

TAK-659 hydrochloride, CAS 1952251-28-3

规格	价格/CNY	货期
1 mg	￥ 329	现货
5 mg	￥ 788	现货
10 mg	￥ 1,160	现货
25 mg	￥ 2,320	现货
50 mg	￥ 3,490	现货
100 mg	￥ 5,120	现货

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其他形式的 TAK-659 hydrochloride:

TAK-659
询价
TAK-659 HCl
询价

选择批次

纯度: 99.63%

纯度: 99.28%

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生物活性

化学信息

存储 & 溶解度

参考文献

相关产品

产品描述	TAK-659 hydrochloride (TAK-659) is a potent and selective inhibitor of spleen tyrosine kinase (SYK) with an IC50 value of 3.2 nM. It is selective against most other kinases, but potent toward both SYK and FLT3.
靶点活性	Syk:3.2 nM
体外活性	In a broad kinase panel, TAK-659 demonstrates a more than 50-fold selectivity for SYK and FLT-3 over 290 other protein kinases. Treatment with TAK-659 inhibits Syk activation and BCR signaling in co-cultured primary CLL cells and Burkitt's lymphoma cells. In primary CLL cells in suspension culture, TAK-659 treatment results in a dose-dependent reduction in the phosphorylation of SykTyr525, Btk, NFκB, ERK1/2 and STAT3 after BCR stimulation. Inhibition of Syk by TAK-659 induces apoptosis of CLL cells and abrogates BCR and co-culture-derived survival signals. TAK-659 inhibits chemotaxis toward BMSC, CXCL12 and CXCL13 in primary CLL cells, and abrogates microenvironment-induced chemoresistance. TAK-659 does not inhibit TCR signaling and molecular features of T cell activation in primary T cells from patients with CLL. In a cell proliferation assay, TAK-659 shows inhibition toward a SYK-dependent cell line (OCI-LY10). the sensitivity to TAK-659 is associated with mutations impacting SYK activity in B cell lymphomas, whereas TAK-659 is not cytotoxic for adherent primary or solid tumor cell lines. In cell viability assays, TAK-659 is shown to be sensitive toward FLT3-ITD dependent cell lines, MV4-11 and MOLM-13 while the WT FLT3 RS4-11 (ALL cell line) and RA1 (Burkitt's Lymphoma cell line) are not sensitive toward TAK-659. In cultured human tumor cells, TAK-659 potently inhibits the growth of hematopoietic-derived cell lines, with a concentration producing half-maximal response (EC50) ranging from 11 to 775 nM in sensitive cell systems (eg, diffuse large B-cell lymphoma, and AML).
体内活性	In the FLT3-dependent MV4-11 xenograft model, TAK-659 shows tumor regression at 60 mg/kg daily after 20 days of dosing. Preliminary plasma and urine PK data show that TAK-659 was absorbed quickly (median Tmax 2-3 hrs), with moderate variability in steady-state exposures (40-50% CV for DN-AUCtau), mean peak/trough ratio of 3.2–4.2, and mean accumulation of 2.1- to 2.6-fold after 15 d QD dosing. Renal clearance (CLr) of unchanged drug accounts for 30–34% of apparent oral clearance, suggesting a CLr contribution of ≥30–34% to TAK-659 systemic clearance. TAK-659 blocks anti-IgD (immune-globulin D antibody) stimulated CD86 expression in mouse peripheral B cells in vivo.
激酶实验	Kinases are prepared in Base Reaction Buffer (20 mM Hepes pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO) and substrate is added with 1.5 mM CaCl2, 16 μg/mL Calmodulin, and 2 mM MnCl2. Varying concentrations of SAR-20347 in DMSO are added to the kinase reaction along with 10 μM 33P-ATP (activity 0.01 μCi/μL final) for IC50 determination[1].
细胞实验	Cell lines: FLT3-dependent cell lines (MV4-11 and MOLM-13)Cells are maintained at 37°C in a humidified atmosphere containing 5-8% CO2. In a panel of hematological and solid tumor cell lines, inhibition of cell viability is determined using the soluble tetrazolium salt, MTS. Cells are seeded in 96-well tissue culture plates and are incubated at 37°C/5% CO2 for 24 hours prior to addition of compounds or DMSO vehicle. After 72 or 96 hours of incubation with compounds, MTS conversion by metabolically active cells is determined by measuring the OD490 nm of the wells using a Thermomax microplate reader. To generate concentration-response curves, cells are treated in duplicate with a range of serial compound dilutions. Prior to addition to cells, compound dilutions are prepared in DMSO. Equal amounts of DMSO are added to cells (final concentration is 0.5%). After background correction and normalization against DMSO-treated cells, EC50 values are calculated by curve-fitting these cell viability results using nonlinear regression analysis.
动物实验	Animal Models: Athymic nude mice. Formulation: 0.5% carboxymethylcellulose (CMC). Dosages: 10,30,60 mg/kg QD. Administration: by oral gavage

别名	TAK-659
分子量	380.85
分子式	C17H22ClFN6O
CAS No.	1952251-28-3

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 2.5 mM

溶液配制表

可选溶剂	浓度体积质量	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.6257 mL	13.1285 mL	26.2571 mL	65.6426 mL

计算器

摩尔浓度计算器

稀释计算器

配液计算器

分子量计算器

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参考文献

1. Lam B, et al. Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK). Bioorg Med Chem Lett. 2016 Dec 15;26(24):5947-5950. 2. Purroy N, et al. Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma-mediated signaling in chronic lymphocytic leukemia cells. Oncotarget. 2017 Jan 3;8(1):742-756. 3. Jie Yu, et al. Journal of Clinicalal Oncology. 2016, 34 (15_suppl).

剂量换算

对于不同动物的给药剂量换算，您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算，可以得到母液配置方法和体内配方的制备方法：比如您的给药剂量是10 mg/kg，每只动物体重20 g，给药体积100 μL，一共给药动物10 只，您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法：2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 50 μL DMSO 主液，加入 300 μL PEG300，混匀澄清，再加 50 μL Tween 80，混匀澄清，再加 600 μL ddH2O, 混匀澄清。

第一步：请输入动物实验的基本信息

剂量

mg/kg

每只动物体重

给药体积

μL

动物数量

第二步：请输入动物体内配方组成，不同的产品配方组成不同，如有配方需求，可先联系我们提供正确的体内配方。

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计算重置

计算结果如下:

工作液浓度: mg/ml;

母液配置方法: mg 药物溶于 μL DMSO (母液浓度为 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 μL DMSO 主液，加入 μL PEG300，混匀澄清，再加 μL Tween 80，混匀澄清，再加 μL ddH₂O, 混匀澄清。

备注:

要按顺序从左向右依次添加助溶剂。可配合物理方法，如涡流、超声波或热水浴使之帮助溶解。

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到，包括如何准备库存溶液，如何存储产品，以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

TAK-659 hydrochloride 1952251-28-3 Angiogenesis Chromatin/Epigenetic JAK/STAT signaling Stem Cells Tyrosine Kinase/Adaptors VEGFR Tyrosine Kinases FLT Syk JAK Spleen Inhibitor Spleen tyrosine kinase Cluster of differentiation antigen 135 inhibit CLL related tyrosine kinase FLT3 TAK659 Fms like tyrosine kinase 3 TAK659 Hydrochloride CD135 TAK 659 hydrochloride TAK-659 TAK659 hydrochloride TAK 659 fms TAK-659 Hydrochloride TAK 659 Hydrochloride inhibitor

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TAK-659 hydrochloride

存储

溶解度

溶液配制表

计算器

输入分子式，点击计算，可计算出产品的分子量。

参考文献

相关产品

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剂量换算

体内实验配液计算器

技术支持

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