CP-724714 是一种高效、选择性口服活性的ErbB2 (HER2)酪氨酸激酶抑制剂,IC50为 10 nM。CP-724714 对 EGFR 激酶有明显的选择性 (IC50=6400 nM)。CP-724714 能抑制完整细胞中 ErbB2 受体的自磷酸化。具有抗肿瘤活性。
生物活性 | CP-724714 is a potent, selective and orally activeErbB2 (HER2)tyrosine kinase inhibitor, with anIC50of 10 nM. CP-724714 displays a marked selectivity againstEGFRkinase (IC50=6400 nM). CP-724714 potently inhibits ErbB2 receptor autophosphorylation in intact cells. Antitumor activities[1][2]. |
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体外研究 (In Vitro) | 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].
Cell Cycle Analysis[1] Cell Line: | erbB2-amplified BT-474 breast cancer cells | Concentration: | 1 μM | Incubation Time: | 24 hours | Result: | Resulted in accumulation of cells in G1 phase and a marked reduction in S-phase cells. |
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体内研究 (In Vivo) | 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].
Animal Model: | Female athymic mice (bearing FRE-erbB2 xenografts)[1] | Dosage: | 3.25-100 mg/kg | Administration: | P.o.; 0.5-8 hours | Result: | Produced a reduction of erbB2 tyrosine phosphorylation in FRE-erbB2 xenografts. |
Animal Model: | Athymic female mice bearing FRE-erbB2 xenografts[1] | Dosage: | 6.25- 100 mg/kg | Administration: | P.o.; q.d; for 8 to 40 day | Result: | Resulted in an inhibition of FRE-erbB2 xenografts. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(106.49 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.1298 mL | 10.6489 mL | 21.2979 mL | 5 mM | 0.4260 mL | 2.1298 mL | 4.2596 mL | 10 mM | 0.2130 mL | 1.0649 mL | 2.1298 mL |
*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。 In Vivo: 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 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。 *以上所有助溶剂都可在本网站选购。
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