Entrectinib (NMS-E628) is a potent, orally available, and CNS-activepan-Trk,ROS1, andALKinhibitor. Entrectinib inhibitsTrkA,TrkB,TrkC, ROS1 and ALK withIC₅₀values of 1, 3, 5, 12 and 7 nM, respectively. Antitumor activity.

Entrectinib (NMS-E628) is found to be exquisitely active in inhibiting the proliferation of a limited number of cell lines: the TRKA-driven colorectal carcinoma cell line KM12 (IC₅₀of 17 nM), the ALK-dependent ALCL cell lines SU-DHL-1, Karpas-299, SUP-M2 and SR-786 (IC₅₀of 20, 31, 41, and 81 nM, respectively), the ALK-dependent NSCLC cell line NCI-H2228 (IC₅₀of 68 nM) and the FLT3-dependent AML cell line MV-4-11 (IC₅₀of 81 nM). Entrectinib potently blocks proliferation of Ba/F3-TEL-TRKB (IC₅₀of 2.9 nM), Ba/F3-TEL-TRKC (IC₅₀of 3.3 nM), and Ba/F3-TEL-ROS1 (IC₅₀of 5.3 nM) cells, with a high degree of selectivity versus parental Ba/F3 cells or those transformed by nontargeted kinases such as ABL and RET, which are inhibited with IC₅₀s in the range of 2 to 3 μM^[1]. Entrectinib significantly inhibits the growth of TrkB-expressing NB cellsin vitro, and it significantly enhances the growth inhibition of Irino-TMZ when used in combination^[2].

Oral administration of entrectinib to tumor-bearing mice induces regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis^[1]. Single agent therapy results in significant tumor growth inhibition in animals treated with entrectinib compared to control animals^[2].

560.64

Solid

C₃₁H₃₄F₂N₆O₂

1108743-60-7

恩曲替尼

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 31 mg/mL(55.29 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： 0.5% MC  0.5%Tween-80

  Solubility: 5 mg/mL (8.92 mM); Suspended solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 5% DMSO    40%PEG300   5%Tween-80   50% saline

  Solubility: ≥ 2.5 mg/mL (4.46 mM); Clear solution
• 3.

  请依序添加每种溶剂： 5% DMSO    95% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (4.46 mM); Clear solution
• 4.

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

  Solubility: ≥ 2.08 mg/mL (3.71 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.71 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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
• 5.

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

  Solubility: 2.08 mg/mL (3.71 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.08 mg/mL (3.71 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 20.8 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
• 6.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.08 mg/mL (3.71 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.71 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。