AZD-3463 (ALK/IGF1R inhibitor) 是一种具有口服活性的ALK/IGF1R抑制剂，对 ALK 作用的Ki值为 0.75 nM。AZD-3463 可诱导神经母细胞瘤细胞凋亡 (apoptosis) 和自噬 (autophagy)。
| 生物活性 | AZD-3463 (ALK/IGF1R inhibitor) is an orally activeALK/IGF1Rinhibitor, with aKiof 0.75 nM for ALK. AZD3463 inducesapoptosisandautophagyin neuroblastoma cells[1][2][3]. |
体外研究
(In Vitro) | AZD-3463 (0-50 μM; 72 h) suppresses the viability and proliferation of both wild type and mutant ALK NB cells[1].
AZD-3463 (10 μM; 0-4 h) effectively inhibits ALK-mediated PI3K/AKT/mTOR signaling and induces apoptosis and autophagy in NB cells[1].
AZD-3463 (0-100 nM; 4 h) inhibits FLT3-ITD-mediated activation of AKT, ERK1/2 and p38 in a dose-dependent manner in MOLM-13 and MV4-11 cells[2].
Cell Proliferation Assay[1] | Cell Line: | IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells | | Concentration: | 0-50 μM | | Incubation Time: | 72 h | | Result: | Inhibited IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells with IC50values of 2.802, 14.55, 11.94, 1.745, 21.34 and 16.49 μM, respectively. |
Cell Autophagy Assay[1] | Cell Line: | IMR-32, NGP , SH-SY5Y and SK-N-AS cells | | Concentration: | 10 μM | | Incubation Time: | 0-4 h | | Result: | Potently inhibited or totally abolished the phosphorylation of Akt Ser473 and RPS6 Thr235/236.
Induced cleavage of the autophagy marker LC3 A/BΙΙ within four hours. |
Apoptosis Analysis[2] | Cell Line: | MOLM-13 and MV4-11 cells | | Concentration: | 0-100 nM | | Incubation Time: | 4 h (pretreat) | | Result: | Selectively inhibited FLT3-ITD but not ligand-induced wild-type FLT3. |
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体内研究
(In Vivo) | AZD3463 (15 mg/kg; i.p.; once daily for 2 days) inhibits tumor growth in different orthotopic NB xenograft mouse models[1].
| Animal Model: | 5 to 6-week-old female athymic Ncr nude mice (SH-SY5Y and NGP xenograft tumors bearing mice)[1]. | | Dosage: | 15 mg/kg | | Administration: | Intraperitoneal injection; once daily for 2 days | | Result: | Showed anti-tumor efficacy in both ALK WT and F1174L mutant orthotropic xenograft mouse models of NB. |
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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 : 20 mg/mL(44.55 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2274 mL | 11.1371 mL | 22.2742 mL | | 5 mM | 0.4455 mL | 2.2274 mL | 4.4548 mL | | 10 mM | 0.2227 mL | 1.1137 mL | 2.2274 mL |
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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
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此方案可获得 ≥ 2 mg/mL (4.45 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 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。 *以上所有助溶剂都可在本网站选购。
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