TAK-659 hydrochloride

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本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1952251-28-3

包装与价格：

包装	价格(元)
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议

产品介绍

TAK-659 hydrochloride 是一种高效、选择性、可逆和口服的脾酪氨酸激酶 (SYK) 和 fms 相关酪氨酸激酶 3 (FLT3) 双重抑制剂，对 SYK 和 FLT3 的 IC50 分别为 3.2 nM 和 4.6 nM。 TAK-659 hydrochloride 在肿瘤细胞中诱导细胞死亡，但在非肿瘤细胞中不诱导细胞死亡，并具有治疗慢性淋巴细胞白血病 (CLL) 的潜力。

Cas No.	1952251-28-3
Canonical SMILES	FC1=C(N[C@@H]2CCCC[C@@H]2N)N=C(C3=CN(C)N=C3)C4=C1CNC4=O.Cl
分子式	C₁₇H₂₂ClFN₆O
分子量	380.85
溶解度	DMSO :< 1 mg/mL (insoluble or slightly soluble);Water : 2 mg/mL (5.25 mM; ultrasonic and adjust pH to 3 with HCl)
储存条件	Store at -20°C
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request
产品描述	TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM. In a cell proliferation assay, TAK-659 shows inhibition toward a SYK-dependent cell line (OCILY10). 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. 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[1]. TAK-659 inhibits the microenvironment-induced activation of Syk and downstream signaling molecules, without inhibiting the protein homologue ZAP-70 in T cells. Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment are abrogated by TAK-659, which furthermore blocks CLL cell migration toward BMSC, CXCL12, and CXCL13[2]. TAK-659 is currently undergoing Phase I clinical trials for advanced solid tumor and lymphoma malignancies, a Phase Ib study in advanced solid tumors in combination with nivolumab, and PhIb/II trials for relapsed/refractory AML. TAK-659 blocks anti-IgD (immune-globulin D antibody) stimulated CD86 expression in mouse peripheral B cells in vivo. In the OCI-LY10 xenograft and DLBCL PHTX-95L (primary human tumor graft from DLBCL patient) mouse models, TAK-659 demonstrates potent tumor growth inhibition (TGI) after 20 days of treatment. In the FLT3-dependent MV4-11 xenograft model, TAK-659 shows tumor regression at 60 mg/kg daily after 20 days of dosing[1]. References: [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.