CEP-37440 是一种口服有效的双重FAK/ALK抑制剂，抑制 FAK 和 ALK 的IC50值分别为 2.3 nM和 3.5 nM。CEP-37440 通过阻断 FAK1 (Tyr 397) 的自磷酸化激酶活性降低细胞增殖。
| 生物活性 | CEP-37440 is a potent, orally active dualFAK/ALKinhibitor withIC50values of 2.3 nM and 3.5 nM forFAKand ALK, respectively. CEP-37440 decreases the cell proliferation by blocking the autophosphorylation kinase activity of FAK1 (Tyr 397)[1][2]. |
| IC50& Target | IC50:2.3 nM (FAK) and 3.5 nM (ALK)[2] |
体外研究
(In Vitro) | CEP-37440 (0-3000 nM; 0-192 h) decreases the proliferation of inflammatory breast cancer (IBC) cells in a dose-dependent manner[1].
CEP-37440 (1000 nM; 0-120 h) decreases phospho-FAK1 (Tyr 397) and maintains its low level over time in FC-IBC02, SUM 190, and KPL4[1].
CEP-37440 (0-3000 nM; Sup-M2 and Karpas-299 cells) induces proapoptotic caspases in a dose-dependent manner[2].
Cell Viability Assay[1] | Cell Line: | FC-IBC02, KPL4, SUM190, MDA-IBC03 and SUM149 cells | | Concentration: | 0, 300, 1000, 2000 and 3000 nM | | Incubation Time: | 0, 24, 48, 72, 96, 120, 144, 168, and 192 hours | | Result: | Reduced the proliferation of three out of five IBC cell lines at low concentration. Inhibited the proliferation almost completely at 3000 nM concentration. |
Western Blot Analysis[1] | Cell Line: | FC-IBC02, SUM 190, and KPL4 cells | | Concentration: | 1000 nM | | Incubation Time: | 0, 48, 72, 96 and 120 hours | | Result: | Decreased phospho-FAK1 by half in FC-IBC02, SUM190, and KPL4 cells after 48 hours. |
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体内研究
(In Vivo) | CEP-37440 (3-55 mg/kg; p.o.; b.i.d and q.d., for 12 d) inhibits breast tumor growth in Sup-M2 xenograftin SCID mice[2].
CEP-37440 (30 mg/kg; p.o; once, for 24 h) inhibits tyrosine phosphorylation in Sup-M2 xenografts mice[2].
CEP-37440 (55 mg/kg; p.o; once, for 24 h) inhibits FAK phosphorylation in CWR22 xenografts in Nude mice[2].
CEP-37440 (1-10 mg/kg; p.o and i.v.; CD-1 mouse, Sprague-Dawley (SD) rats) has good pharmacokinetic parameters[2].
| Animal Model: | SCID/Beige with Sup-M2 xenografts[2] | | Dosage: | 3 mg/kg (b.i.d), 10 mg/kg (b.i.d), 30 mg/kg (b.i.d and q.d. ), and 55 mg/kg (q.d.) | | Administration: | Oral administration; b.i.d and q.d., for 12 days | | Result: | Inhibited tumor growth in a dose-dependent manner. |
| Animal Model: | SCID/Beige with Sup-M2 xenografts and Nu/Nu mice female with Sup-M2 xenografts[2] | | Dosage: | 30 mg/kg | | Administration: | Oral administration; once, for 24 hours | | Result: | Decreased NPM-ALK phosphorylation (>85%). |
| Animal Model: | Nu/Nu mice female with CWR22 xenografts[2] | | Dosage: | 55 mg/kg | | Administration: | Oral administration; once, for 24 hours | | Result: | Inhibited FAK phosphorylation in a time-dependent manner. |
| Animal Model: | CD-1 mouse, Sprague-Dawley (SD) rats[2] | | Dosage: | 1, 5, and 10 mg/kg | | Administration: | Oral administration (5, and 10 mg/kg), intravenous injection (1 mg/kg); once | | Result: | 1.19 | PK parameter | CD-1 mouse | SD rat | | iv | dose (mg/kg) | 1 | 1 | | iv | t1/2(h) | 3.0 | 2 | | iv | AUC0-∞(ng*h/mL) | 1612 | 4005 | | iv | Vd (L/kg) | 2.7 | 0.8 | | iv | CL (mL/min/kg) | 10 | 4 | | po | dose (mg/kg) | 10 | 5 | | po | Cmax(ng/mL) | 1533 | 1340 | | po |
| | Clinical Trial | | | 分子量 | | | 性状 | | | Formula | | | CAS 号 | | | 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 |
| | 溶解性数据 | In Vitro: DMSO : 100 mg/mL(172.38 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.7238 mL | 8.6189 mL | 17.2378 mL | | 5 mM | 0.3448 mL | 1.7238 mL | 3.4476 mL | | 10 mM | 0.1724 mL | 0.8619 mL | 1.7238 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 (4.31 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.31 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 (4.31 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.31 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 (4.31 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.31 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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