TAK-659 hydrochloride

SKU: orb1225787

Description

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.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1952251-28-3
• MW: 380.852
• Purity: >98% (HPLC)
• Formula: C₁₇H₂₂ClFN₆O
• SMILES: CN1C=C(C=N1)C2=NC(=C(C3=C2C(=O)NC3)F)NC4CCCCC4N.Cl
• Target: Syk
• Solubility: 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 )

Bioactivity

• 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. Animal model: LMP2A/MYC double transgenic mice. Dosage: 100 mg/kg/day. Administration: Oral gavage; for 10 days. Result: Inhibited LMP2A-induced tumor cell survival In vivo.
• 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. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Mivavotinib | TAK 659 | TAK659

Quick Database Links

Gene Symbol

Syk