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TAK-659 HCl

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Chemical Structure| 1952251-28-3 同义名 : TAK-659;TAK-659 hydrochloride
CAS号 : 1952251-28-3
货号 : A863648
分子式 : C17H22ClFN6O
纯度 : 99%+
分子量 : 380.848
MDL号 : MFCD31544322
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

H2O: 2 mg/mL(5.25 mM)，配合低频超声，并调节pH至3
动物实验配方：
生物活性
靶点

  • FLT3

    FLT3, IC50:4.6 nM

  • Syk

    Syk, IC50:3.2 nM
描述 Spleen Tyrosine Kinase (SYK) is a non-receptor cytoplasmic tyrosine kinase that is primarily expressed in hematopoietic cells. SYK is a key mediator for a variety of inflammatory cells, including B cells, mast cells, macrophages and neutrophils[3]. TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM[3]. In a cell proliferation assay, TAK-659 shows inhibition toward a SYK-dependent cell line (OCILY10)[3]. TAK-659 inhibited 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 were abrogated by TAK-659, which furthermore blocked CLL cell migration toward BMSC, CXCL12, and CXCL13[4]. 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[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.63mL

0.53mL

0.26mL

13.13mL

2.63mL

1.31mL

26.26mL

5.25mL

2.63mL
参考文献

[1]Purroy N, Carabia J, 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.

[2]Lam B, Arikawa Y, 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.

[3]Lam B, Arikawa Y, Cramlett J, Dong Q, de Jong R, Feher V, Grimshaw CE, Farrell PJ, Hoffman ID, Jennings A, Jones B, Matuszkiewicz J, Miura J, Miyake H, Natala SR, Shi L, Takahashi M, Taylor E, Wyrick C, Yano J, Zalevsky J, Nie Z. 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. doi: 10.1016/j.bmcl.2016.10.087. Epub 2016 Nov 2. PMID: 27839918.

[4]Purroy N, Carabia J, Abrisqueta P, Egia L, Aguiló M, Carpio C, Palacio C, Crespo M, Bosch F. 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. doi: 10.18632/oncotarget.13557. PMID: 27888629; PMCID: PMC5352193.