Tandutinib hydrochloride (MLN518 hydrochloride) 是一种有效和选择性的 FLT3 的抑制剂，其 IC50 为 0.22 μM，并且还抑制 c-Kit 和 PDGFR，其 IC50 分别为 0.17 μM 和 0.20 μM。Tandutinib hydrochloride 可用于治疗急性骨髓性白血病，并具有穿越血脑屏障的能力。
货号:ajcx15490
CAS:N/A
分子式:C31H43ClN6O4
分子量：599.16
溶解度:DMSO: ≥ 100 mg/mL (166.90 mM); H2O: 100 mg/mL (166.90 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Tandutinib hydrochloride (MLN518 hydrochloride) is a potent and selective inhibitor of the FLT3 with an IC50 of 0.22 μM, and also inhibits c-Kit and PDGFR with IC50s of 0.17 μM and 0.20 μM, respectively. Tandutinib hydrochloride can be used to treat acute myelogenous leukemia (AML)[1][2]. Tandutinib hydrochloride has the ability to cross the blood-brain barrier[3].

Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants[1].Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells[1].In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50 of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib[1].Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways[1]. Apoptosis Analysis[1] Cell Line: Molm-14 and THP-1 AML cells

Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days[1]. Animal Model: Athymic nude mice injected with Ba/F3 cells[1]

[1]. Kelly LM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell. 2002 Jun;1(5):421-32. [2]. Griswold IJ, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood. 2004 Nov 1;104(9):2912-8. [3]. Yang JJ, et al. P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor. Drug Metab Lett. 2010 Dec;4(4):201-12.