CP-724714 is a potent, selective and orally active ErbB2 (HER2) tyrosine kinase inhibitor, with an IC₅₀ of 10 nM. CP-724714 displays a marked selectivity against EGFR kinase (IC₅₀=6400 nM). CP-724714 potently inhibits ErbB2 receptor autophosphorylation in intact cells. Antitumor activities^[1][2].

CP-724714 is >1,000-fold less potent for insulin receptor, insulin-like growth factor-I receptor, platelet-derived growth factor β, vascular endothelial growth factor 2, Abl, Src, c-Met, JNK-2, JNK-3, ZAP-70, Cdk-2, and Cdk-5^[1].
CP-724714 potently reduces the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain at a concentration as low as 50 nmol/L (IC₅₀=32 nM) but is markedly less potent against EGFR^[1].
CP-724714 (1 μM; 24 hours) induces G1 cell cycle block in vitro in erbB2-overexpressing BT-474 human breast carcinoma 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.

CP-724714 (3.25-100 mg/kg; p.o.; 0.5-8 hours) results in a concentration-dependent reduction of ErbB2 receptor phosphorylation^[1].
CP-724714 (6.25-100 mg/kg; p.o.; q.d; for 8 to 40 day) inhibits FRE-erbB2 xenograft growth^[1].
CP-724714 (Athymic, female FRE-erbB2 xenograft-bearing mice; 30 or 100 mg/kg; p.o.) treatments results in a time- and dose- dependent induction of apoptosis, which was evident as early as 4 to 8 h after dosing. Approximately 75% more tumor cells exhibited apoptotic changes in the 100 mg/kg treatment group compared with vehicle control group at 8 h after dosing. CP-724714 induces regression of BT-474 tumors and significant inhibition in a number of other human tumor xenografts. Additionally, CP-724714 showed a favorable nonclinical toxicity profile with no apparent effects on cardiac tissue^[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.

469.53

C₂₇H₂₇N₅O₃

383432-38-0

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL (106.49 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°C, 6 months; -20°C, 1 month。-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： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.32 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-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.32 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.32 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]. Jani JP, et al. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer Res, 2007, 67(20), 9887-9893.

  [2]. Feng B, et al. Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714. Toxicol Sci, 2009, 108(2), 492-500.