AST 487 is aRETkinase inhibitor withIC₅₀of 880 nM, inhibitsRETautophosphorylation and activation of downstream effectors, also inhibitsFlt-3withIC₅₀of 520 nM.

IC50: 880 nM (RET), 170 nM (KDR), 790 nM (Flt-4), 500 nM (c-Kit), 520 nM (Flt-3), 20 nM (Abl)^[1]

A number of other kinases are also similarly inhibited by AST 487 (NVP-AST487) in the in vitro kinase assays, including KDR (IC₅₀=170 nM), Flt-4 (IC₅₀=790 nM), Flt-3 (IC₅₀=520 nM), c-Kit (IC₅₀=500 nM), and c-Abl (IC₅₀=20 nM). AST 487 potently inhibits the growth of human thyroid cancer cell lines with activating mutations ofRETbut not of lines withoutRETmutations. Both GDNF/GFRα1 and persephin-induced calcitonin mRNA are markedly inhibited by coincubation with 100 nM of AST 487 in MTC-M cells^[1]. AST 487 is a novel, mutant FLT3 inhibitor. AST 487 is tested in biochemical assays for inhibition of Flt-3 kinase activity. The K_iis determined to be 0.12 μM. Besides Flt-3, NVP-AST487 inhibits RET, KDR, c-Kit, and c-Abl kinase with IC₅₀values below 1 μM. Treatment of FLT3-ITD-Ba/F3 cells and D835Y-Ba/F3 cells with AST 487 potently inhibits cellular proliferation (IC₅₀<5 nm). ast 487 treatment of flt3-itd-baf3 cells with 0.01 μm results in complete cell killing compare approximately 50% aml patient samples at the same concentration^[2].

After a single oral administration of 15 mg/kg of AST 487 to OF1 mice, a mean peak plasma level (C_max) of 0.505±0.078 μM SE is achieved after 0.5 h. Similar levels of AST 487 are found in the plasma of mice up to 6 h after oral administration, with a C_lastof 21±4 nM at 24 h. The oral bioavailability is calculated to be 9.7% with a t_1/2terminal elimination of 1.5 h^[1].

529.56

Solid

C₂₆H₃₀F₃N₇O₂

630124-46-8

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL(188.84 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (4.72 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.72 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (4.72 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.72 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (4.72 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.72 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。