TAK-659 hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

TAK-659 盐酸盐（Mivavotinib，TAK659）是一种有效的、选择性的、口服的 SYK 抑制剂，IC50 为 3.2 nM。

TAK-659 hydrochloride (Mivavotinib, TAK659) is a potent, selective and orally available SYK inhibitor with IC50 of 3.2 nM; displays 36, 42 and 23-fold selectivity over JAK3, ZAP70 and VEGFR2, respectively; also potently inhibits FLT-3; inhibits cellular proliferation in SYK-dependent DLBCL and FLT3-dependent AML cell lines, demonstrates potent tumor growth inhibition in the FLT3-dependent MV4-11 xenograft models.Blood Cancer Phase 2 Clinical(In Vitro):TAK-659 hydrochloride inhibits cellular proliferation in SYK-dependent DLBCL and FLT3-dependent AML cell lines.TAK-659 hydrochloride (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.TAK-659 hydrochloride (0.01-10 μM; 1 hour) stimulates expression of phospho-Syk at Tyr525 and Tyr352 and phospho-ERK1/2 increased in Ramos cells.(In Vivo):TAK-659 hydrochloride (100 mg/kg/day; p.o.; daily, for 10 days) treatment totally abrogates splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments.TAK-659 hydrochloride treatment kills tumor cells, but not host cells within the spleen and tumors.TAK-659 hydrochloride treatment abrogates metastasis of tumor cells into bone marrow.

TAK-659 hydrochloride inhibits cellular proliferation in SYK-dependent DLBCL and FLT3-dependent AML cell lines.TAK-659 hydrochloride (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.TAK-659 hydrochloride (0.01-10 μM; 1 hour) stimulates expression of phospho-Syk at Tyr525 and Tyr352 and phospho-ERK1/2 increased in Ramos cells. Apoptosis Analysis 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 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.

TAK-659 hydrochloride (100 mg/kg/day; p.o.; daily, for 10 days) treatment totally abrogates splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments.TAK-659 hydrochloride treatment kills tumor cells, but not host cells within the spleen and tumors.TAK-659 hydrochloride treatment abrogates metastasis of tumor cells into bone marrow. Animal Model:LMP2A/MYC double transgenic mice Dosage:100 mg/kg/day Administration:Oral gavage; for 10 daysResult:Inhibited LMP2A-induced tumor cell survival in vivo.

Mivavotinib | TAK 659 | TAK659

Angiogenesis

Syk

FLT3|JAK3|Syk|VEGFR2|ZAP70

Cancer

Blood cancer

1952251-28-3

380.852

C17H22ClFN6O

>98% (HPLC)

DMSO: <1 mg/mL; Ethanol: <1 mg/mL; Water: 4 mg/mL (10.5 mM), warmed （ < 1 mg/ml refers to the product slightly soluble or insoluble )

CN1C=C(C=N1)C2=NC(=C(C3=C2C(=O)NC3)F)NC4CCCCC4N.Cl

6-(((1R,2S)-2-aminocyclohexyl)amino)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one hydrochloride

(-20℃)

With Ice Pack

≥ 2 years