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 可用于急性骨髓性白血病，并具有穿越血脑屏障的能力。

Tandutinib hydrochloride (MLN518 hydrochloride) is a potent and selective inhibitor of the FLT3 with an IC 50 of 0.22 μM, and also inhibits c-Kit and PDGFR with IC 50 s of 0.17 μM and 0.20 μM, respectively. Tandutinib hydrochloride can be used for 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 IC 50 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 ( IC 50 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 IC 50 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 Concentration: 1 μM Incubation Time: 24 hours, 48 hours, 72 hours, 96 hours Result: Induced apoptosis in FLT3-ITD-positive AML cells. Western Blot Analysis [1] Cell Line: Ba/F3 cells Concentration: 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation Time: 30 minutes Result: In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.

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] Dosage: 60 mg/kg Administration: Oral gavage; daily; for 35 days Result: Caused a statistically significant increase in survival that was extended on average by 20 days.

C31H43ClN6O4

599.16

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years