Alectinib
别名: AF-802, RG-7853,CH5424802 中文名称：阿来替尼,艾乐替尼
Alectinib是一种有效的ALK抑制剂，在无细胞试验中IC50为1.9 nM，对L1196M突变型敏感，对ALK比PF-02341066， NVP-TAE684和PHA-E429选择性高。
Alectinib Chemical Structure
CAS: 1256580-46-7
产品质控
批次：
纯度：
99.99%
99.99
Alectinib相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| NIH/3T3 | Antitumor assay | 50 mg/kg | 10 days | Antitumor activity against mouse NIH/3T3 cells expressing EML4-ALK L1196M mutant xenografted in nude mouse assessed as tumor stasis at 50 mg/kg, po qd administered for 10 days | 27131066 |
| NIH/3T3 | Antitumor assay | 50 mg/kg | 10 days | Antitumor activity against mouse NIH/3T3 cells expressing EML4-ALK L1196M mutant xenografted in nude mouse assessed as partial tumor regression at 50 mg/kg, po qd administered for 10 days | 27131066 |
| MKN-45 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| NCI-H1993 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| NCI-H2009 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| Calu-1 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| NCI-H23 | Growth inhibitory assay | ~10 μM | IC50=3600 nM | 21575866 | |
| PC-1 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| Calu-3 | Growth inhibitory assay | ~10 μM | IC50=>10,000 nM | 21575866 | |
| NCI-H2228 | Growth inhibitory assay | ~10 μM | IC50=53 nM | 21575866 | |
| SK-N-FI | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| KELLY | Growth inhibitory assay | ~10 μM | IC50=62 nM | 21575866 | |
| NB-1 | Growth inhibitory assay | ~10 μM | IC50=4.5 nM | 21575866 | |
| HDLM-2 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| SR | Growth inhibitory assay | ~10 μM | IC50=6.9 nM | 21575866 | |
| KARPAS-299 | Growth inhibitory assay | ~10 μM | IC50=3 nM | 21575866 | |
| NCI-H2228 | Kinase assay | ~1 μM | prevents autophosphorylation of ALK | 21575866 | |
| SNU-5 | Growth inhibitory assay | ~10 μM | IC50=1800 nM | 21575866 | |
| KATO-III | Growth inhibitory assay | ~10 μM | IC50=7900 nM | 21575866 | |
| SK-BR-3 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| BT-483 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| PC-3 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| 22Rv1 | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| U-87 MG | Growth inhibitory assay | ~10 μM | IC50>10,000 nM | 21575866 | |
| H3122 | Growth inhibitory assay | ~10 μM | IC50=33 nM | 25096400 | |
| LC-2/ad | Apoptosis assay | ~1 μM | induces apoptosis | 25349307 | |
| LC-2/ad | Function assay | ~1 μM | inhibits the MAPK signaling pathway | 25349307 | |
| Ba/F3 | Function assay | ~1 μM | suppresses phosphorylation of ERK and increases the abundance of BIM | 25349307 | |
| SNU-2535 | Growth inhibitory assay | ~10 μM | IC50=33.1 nM | 26849637 | |
| SNU-2535 | Kinase assay | ~1 μM | inhibits the phosphorylation of ALK and its downstream molecules ERK1/2 and AKT | 26849637 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.002 μM. | 26568289 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK S1206Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.002 μM. | 26568289 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.002 μM. | 26568289 | |
| KARPAS299 | Antiproliferative assay | 96 hrs | Antiproliferative activity against human KARPAS299 cells after 96 hrs by cell counting assay, IC50 = 0.003 μM. | 22225917 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.003 μM. | 26568289 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK G1269A mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.009 μM. | 26568289 | |
| NCI-H3122 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human NCI-H3122 cells after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.009 μM. | 26568289 | |
| KARPAS299 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human KARPAS299 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.015 μM. | 27131066 | |
| NCI-H3122 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0174 μM. | 27131066 | |
| SUP-M2 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SUP-M2 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0179 μM. | 27131066 | |
| NCI-H3122 | Function assay | 72 hrs | Inhibition of ALK expressed in human NCI-H3122 cells assessed as cell growth inhibition after 72 hrs by SRB/CCK-8 assay, IC50 = 0.019 μM. | 27131066 | |
| NCI-H3122 | Antiproliferative assay | 72 hrs | Antiproliferative activity against ALK-dependent human NCI-H3122 cells after 72 hrs, IC50 = 0.019 μM. | 26476749 | |
| SU-DHL1 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SU-DHL1 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0205 μM. | 27131066 | |
| NIH/3T3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against mouse NIH/3T3 cells expressing wild type EML4-ALK after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0323 μM. | 27131066 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK 1151Tins mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.072 μM. | 26568289 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.09 μM. | 26568289 | |
| NIH/3T3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against mouse NIH/3T3 cells expressing EML4-ALK L1196 mutant after 72 hrs by SRB/CCK-8 assay, IC50 = 0.132 μM. | 27131066 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK L1152R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.169 μM. | 26568289 | |
| Ba/F3 | Function assay | 72 hrs | Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.207 μM. | 26568289 | |
| DFCI114 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human DFCI114 cells expressing EML4-ALK G1269A mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.207 μM. | 26568289 | |
| CHLA20 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human CHLA20 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.43 μM. | 26568289 | |
| Kelly | Antiproliferative assay | 72 hrs | Antiproliferative activity against human Kelly cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.434 μM. | 26568289 | |
| DFCI76 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human DFCI76 cells expressing EML4-ALK L1152R mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.511 μM. | 26568289 | |
| LAN5 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human LAN5 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.617 μM. | 26568289 | |
| SMS-KCNR | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SMS-KCNR cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.765 μM. | 26568289 | |
| SK-N-SH | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SK-N-SH cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.872 μM. | 26568289 | |
| SH-SY5Y | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SH-SY5Y cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.15 μM. | 26568289 | |
| SK-N-BE(2) | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SK-N-BE(2) cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.554 μM. | 26568289 | |
| LAN1 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human LAN1 cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 2.004 μM. | 26568289 | |
| SK-N-AS | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SK-N-AS cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 2.139 μM. | 26568289 | |
| SK-N-FI | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SK-N-FI cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 2.401 μM. | 26568289 | |
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Alectinib是一种有效的ALK抑制剂，在无细胞试验中IC50为1.9 nM，对L1196M突变型敏感，对ALK比PF-02341066， NVP-TAE684和PHA-E429选择性高。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | CH5424802作用于ALK 为ATP竞争性的，解离常数(KD)为2.4 nM。CH5424802对ALK 和L1196M 具有强大的抑制效果，Ki分别为0.83 和1.56 nM。 CH5424802 作用于表达EML4-ALK的NCI-H2228 NSCLC细胞，抑制ALK自磷酸化。 CH5424802 也抑制STAT3 和AKT,而不是 ERK1/2的磷酸化。CH5424802 完全抑制STAT3在Tyr705位点的磷酸化。CH5424802优先有效作用于表达EML4-ALK的 NCI-H2228细胞，而不作用于融合ALK的阴性 NSCLC细胞系，包括单层培养的HCC827细胞(EGFR外显子19缺失), A549细胞(KRAS突变), 或NCI-H522细胞(EGFR 野生型, KRAS 野生型, 和ALK野生型)。CH5424802作用于 NCI-H2228球体细胞，引起凋亡标记—caspase-3/7样激活。CH5424802抑制含NPM-ALK融合蛋白的两种淋巴瘤细胞, KARPAS-299和SR生长,为不影响不含ALK融合的 HDLM-2淋巴瘤细胞生长。[1] CH5424802 作用于KARPAS-299具有高度靶向选择性和更强的抗增殖活性。CH5424802抑制KAPRAS-299，IC50为3 nM, 抑制KDR， IC50为1.4 μM。CH5424802代谢稳定性很高。[2] | |||
|---|---|---|---|---|
| 激酶实验 | 体外激酶抑制检测 | |||
| 在CH5424802存在时，通过时间分辨荧光共振能量转移（TR-FRET）分析或荧光偏振（FP）法测量磷酸化各种底物肽的能力，而测评抑制各种激酶（除了MEK1和 Raf-1）的能力。在CH5424802存在时，通过定量分析重组ERK2 蛋白对底物的磷酸化而测评对MEK1的抑制活性。在 CH5424802存在时，通过测定激酶磷酸化MEK1的能力而测评对Raf-1的抑制活性。 | ||||
| 细胞实验 | 细胞系 | NSCLC, A549 和 HCC827 细胞 | ||
| 浓度 | 0-1 μM | |||
| 孵育时间 | 5天 | |||
| 方法 | NSCLC, A549 和HCC827细胞接种在96孔板中过夜，与不同浓度CH5424802按指定时间温育。球体细胞生长抑制实验中，细胞接种在球板上，温育过夜，然后在指定时间用化合物处理。通过发光细胞活性检测存活细胞。使用Caspase-Glo 3/7 检测试剂盒进行Caspase-3/7检测。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | pALK / ALK / pAKT / AKT / pERK / ERK / pS6 / S6 PARP / cleaved PARP / Akt / caspase 3 / Cleaved caspase 3 pROS1 / ROS1 / pSTAT3 / STAT3 p-EGFR Tyr1068 / EGFR / p-HER3 Tyr1222 / HER3 / p-IGF-1R Tyr1135 / IGF-1R |
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25228534 | |
| Growth inhibition assay | Cell viability |
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25228534 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | CH5424802口服处理，抑制肿瘤生长，这种作用存在剂量依赖性，ED50为0.46 mg/kg。CH5424802按20 mg/kg剂量处理，引起肿瘤快速衰退，衰退达168%,处理11天后(在第28天)每个鼠中的肿瘤体积<30 mm3, 维持有效的抗肿瘤效果，且在4周的无药处理期间，不会出现肿瘤再生长。CH5424802 处理小鼠的半衰期和口服生物有效性分别为8.6 小时和 70.8%。按6 mg/kg重复剂量处理，在2,7,和24小时后，平均血浆水平达到1.7,1.5,和0.3 nM。CH5424802处理抑制肿瘤生长。CH5424802按20 mg/kg剂量处理 KARPAS-299 和 NB-1，在第20天，肿瘤生长抑制达 119% 和104%。CH5424802 抑制STAT3磷酸化，这种作用存在剂量依赖性(2-20 mg/kg)。CH5424802处理的移植瘤中，观察到AKT磷酸化部分降低。[1] | |
|---|---|---|
| 动物实验 | Animal Models | 携带NCI-H2228细胞的 SCID 或裸鼠 |
| Dosages | 20 mg/kg | |
| Administration | 口服处理 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT05987956 | Not yet recruiting | Non-small Cell Lung Cancer |
Han Xu M.D. Ph.D. FAPCR Sponsor-Investigator IRB Chair|Medicine Invention Design Inc |
March 8 2024 | Phase 2|Phase 3 |
| NCT05987644 | Recruiting | Lung Cancer|NSCLC|Brain Metastases |
Joshua Palmer|Genentech Inc.|Hoosier Cancer Research Network |
March 7 2024 | Phase 1|Phase 2 |
| NCT05710133 | Enrolling by invitation | NSCLC |
The Netherlands Cancer Institute |
February 1 2024 | Not Applicable |
| NCT05770037 | Recruiting | Solid Tumor|Haematological Malignancy|Malignant Neoplasm|Lymphoproliferative Disorders|Neoplasms by Histologic Type|Neoplasms by Site|Cancer|Anaplastic Large Cell Lymphoma|Lymphoma|Renal Cell Carcinoma|Neuroblastoma |
Cancer Research UK|University of Manchester|University of Birmingham|Royal Marsden NHS Foundation Trust|Hoffmann-La Roche |
December 18 2023 | Phase 2|Phase 3 |
| NCT05525338 | Recruiting | Drug Monitoring|Carcinoma Non-Small-Cell Lung|Lung Cancer|Anaplastic Lymphoma Kinase Gene Mutation|Anaplastic Lymphoma Kinase Gene Translocation |
University Medical Center Groningen|Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Erasmus Medical Center|Maastricht University Medical Center|Radboud University Medical Center|The Netherlands Cancer Institute|Leiden University Medical Center |
March 23 2022 | Phase 4 |
| NCT04774718 | Recruiting | ALK Fusion-positive Solid or CNS Tumors |
Hoffmann-La Roche |
September 14 2021 | Phase 1|Phase 2 |
化学信息&溶解度
| 分子量 | 482.62 | 分子式 | C30H34N4O2 |
| CAS号 | 1256580-46-7 | SDF | Download Alectinib SDF |
| Smiles | CCC1=CC2=C(C=C1N3CCC(CC3)N4CCOCC4)C(C5=C(C2=O)C6=C(N5)C=C(C=C6)C#N)(C)C | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 3 mg/mL ( (6.21 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解配方 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | |||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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