TAK-659

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

TAK-659 

TAK-659 是一种高效选择性、可逆的，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。TAK-659 能诱导肿瘤细胞死亡而不作用于非肿瘤细胞，具有研究慢性淋巴细胞白血病 (CLL) 的潜力。

TAK-659

TAK-659 Chemical Structure

CAS No. : 1312691-33-0

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TAK-659 的其他形式现货产品:

TAK-659 hydrochloride

生物活性

TAK-659 is a highly potent, selective, reversible and orally available dual inhibitor of spleen tyrosine kinase (SYK) and fms related tyrosine kinase 3 (FLT3), with an IC50 of 3.2 nM and 4.6 nM for SYK and FLT3, respectively. TAK-659 induces cell death in tumor cells but not in nontumor cells, and with potential for the treatment of chronic lymphocytic leukemia (CLL)[1][2][3][4].

IC50 & Target

IC50: 3.2 nM (Syk), 4.6 nM (FLT3)[1]
体外研究
(In Vitro)

TAK-659 inhibits cellular proliferation in SYK-dependent DLBCL and FLT3-dependent AML cell lines[1][3].
TAK-659 (5 µM; 1-24 hours) induces Casp3 activation in the LMP2A/MYC cells which was readily apparent at 4 h and reached maximum levels at 8 h of treatment[4].
TAK-659 (0.01-10 μM; 1 hour) stimulates expression of phospho-Syk at Tyr525 and Tyr352 and phospho-ERK1/2 increased in Ramos cells[2].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Apoptosis Analysis[4]

Cell Line: LMP2A/MYC cells
Concentration: 5 µM
Incubation Time: 1 hour, 2 hours, 4 hours, 8 hours, 24 hours
Result: Induced apoptosis in LMP2A/MYC lymphoma cells.

Western Blot Analysis[2]

Cell Line: Ramos cells
Concentration: 0.01 μM,0.1 μM,1 μM,10 μM
Incubation Time: 1 hour
Result: Enhanced expression of phospho-Syk at Tyr525 and Tyr352 and phospho-ERK1/2 in stimulated Ramos cells.

体内研究
(In Vivo)

TAK-659 (100 mg/kg/day; p.o.; for 10 days) treatment totally abrogates splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments[4].
TAK-659 treatment kills tumor cells, but not host cells within the spleen and tumors[4].
TAK-659 treatment abrogates metastasis of tumor cells into bone marrow[4].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: LMP2A/MYC double transgenic mice[4]
Dosage: 100 mg/kg/day
Administration: Oral gavage; for 10 days
Result: Inhibited LMP2A-induced tumor cell survival in vivo.

Clinical Trial

分子量

344.39

Formula

C17H21FN6O
CAS 号

1312691-33-0
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
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. Anti-tumor activity of TAK-659, a dual inhibitor of SYK and FLT-3 kinases, in AML models. Journal of Clinical Oncology 34, no. 15_suppl.

    [4]. Cen O, et al. Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma. mSphere. 2018 Aug 22;3(4).

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