Ceritinib dihydrochloride (LDK378 dihydrochloride) is a selective, orally bioavailable and ATP-competitive ALK tyrosine kinase inhibitor with an IC₅₀ of 200 pM. Ceritinib dihydrochloride (LDK378 dihydrochloride) also inhibits IGF-1R, InsR, and STK22D with IC₅₀ values of 8, 7, and 23 nM, respectively. Ceritinib dihydrochloride (LDK378 dihydrochloride) shows great antitumor potency^[1][2].

IC50: 0.2 nM (ALK), 8 nM (IGF-1R), 7 nM (InsR), 23 nM (STK22D)^[1]

Ceritinib (LDK378) shows great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells with IC₅₀ of 26.0 nM and 22.8 nM, compared with IC₅₀ of 319.5 nM and 2477 nM in Ba/F3-Tel-InsR and Ba/F3-WT cells^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Ceritinib (LDK378) is designed to reduce the possibility of forming reactive metabolites and shows undetectable levels of glutathione (GSH) adducts (<1%) in liver microsomes. Ceritinib (LDK378) has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. Ceritinib (LDK378) exhibits low plasma clearance in animals (mouse, rat, dog and monkey) compared to liver blood flow, with the oral bioavailability of above 55% in mouse, rat, dog and monkey. Ceritinib (LDK378) induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. Ceritinib (LDK378) shows no impact on insulin levels or plasma glucose utilization in the mouse upon chronic dosing up to 100 mg/kg^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

631.06

C₂₈H₃₈Cl₃N₅O₃S

1380575-43-8

色瑞替尼二盐酸盐；双盐酸盐色瑞替尼

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : 100 mg/mL (158.46 mM; Need ultrasonic)

H₂O : 10 mg/mL (15.85 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 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： PBS

  Solubility: 100 mg/mL (158.46 mM); Clear solution; Need ultrasonic
• 2.

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

  Solubility: 2.5 mg/mL (3.96 mM); Clear solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (3.96 mM) 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

• 3.

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

  Solubility: ≥ 2.5 mg/mL (3.96 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.96 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 μL 20% 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (3.96 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.96 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。

• [1]. Marsilje TH, et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013, Jun 6.

  [2]. Rothschild SI. Ceritinib-a second-generation ALK inhibitor overcoming resistance in ALK-rearranged non-small celllung cancer. Transl Lung Cancer Res. 2014 Dec;3(6):379-81.