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TAK-659 HCl
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。
TAK-659 HCl图片
CAS NO:1952251-28-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 380.85
Formula C17H21FN6 .HCl
CAS No. 1952251-28-3 (HCl);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: Insoluble
Water: 4 mg/mL warmed (10.5 mM)
Ethanol: Insoluble
SMILES CodeFC1=C(N[C@@H]2CCCC[C@@H]2N)N=C(C3=CN(C)N=C3)C4=C1CNC4=O.Cl
SynonymsTAK659, TAK-659, TAK 659, TAK-659 HCl, TAK659 hydrochloride
实验参考方法
In Vitro

In vitro activity: 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. 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.


Kinase Assay:


Cell Assay: 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.

In Vivo 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
Animal model Athymic nude mice
Formulation & Dosage 0.5% carboxymethylcellulose (CMC); 10, 30, 60 mg/kg QD; by oral gavage
References

Bioorg Med Chem Lett. 2016 Dec 15;26(24):5947-5950; Oncotarget. 2017 Jan 3;8(1):742-756;