Alectinib Hydrochloride
(Synonyms: 艾乐替尼盐酸盐; CH5424802 Hydrochloride; RO5424802 Hydrochloride; AF-802 Hydrochloride) 目录号 : GC35280
一键复制产品信息
Alectinib Hydrochloride是一种强效、选择性、可口服的ALK抑制剂，IC50值为1.9nM，Kd值为2.4nM。
Cas No.:1256589-74-8
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Alectinib Hydrochloride is a potent, selective, and orally available ALK inhibitor with an IC50 value of 1.9nM and a Kd value of 2.4nM[1]. Alectinib Hydrochloride suppresses the L1196M-mutant ALK with an IC50 of 1.56nM[2]. Alectinib Hydrochloride increases the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells, and stimulates ATPase activity and competed with substrates of ABCB1 or ABCG2[3]. Alectinib Hydrochloride has been widely used to inhibit the growth of lung cancer cells with ALK mutations[4].
In vitro, Alectinib Hydrochloride treatment for 48 hours significantly inhibited the proliferation of H2228 cells and ABC-11 cells, with IC50 values of 0.03μM and 0.13μM, respectively[5]. Treatment with 30nM Alectinib Hydrochloride for 48 hours significantly inhibited ALK-mediated neurite growth in PC12 cells[6]. Treatment with 10μM Alectinib Hydrochloride for 48 hours induced apoptosis in U87MG cells, inhibited the tyrosine phosphorylation of STAT3, and activated the tyrosine phosphorylation of Janus kinase 2 (JAK2)[7].
In vivo, Alectinib Hydrochloride treatment at a single dose of 50mg/kg via intraperitoneal injection for 24 hours significantly reduced cerebral infarction and neurological deficits in the ischemic stroke mouse model, as well as the loss of cerebral vascular integrity and damage to the blood-brain barrier[8]. Oral administration of 10mg/kg of Alectinib Hydrochloride daily for 4 weeks significantly inhibited tumor growth in a H3122 cell-xenograft mouse model, without affecting the body weight of the mice[9].
References:
[1] Madlool D T, Al-Ani I, Ata T, et al. Solubility, pH-Solubility Profile, pH-Rate Profile, and Kinetic Stability of the Tyrosine Kinase Inhibitor, Alectinib[J]. Pharmaceuticals, 2024, 17(6): 776.
[2] Song Z, Wang M, Zhang A. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance[J]. Acta Pharmaceutica Sinica B, 2015, 5(1): 34-37.
[3] Yang K, Chen Y, To K K W, et al. Alectinib (CH5424802) antagonizes ABCB1-and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo[J]. Experimental & molecular medicine, 2017, 49(3): e303-e303.
[4] Yoshimura Y, Kurasawa M, Yorozu K, et al. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation: efficacy of alectinib against ALK G1269A mutated cells[J]. Cancer chemotherapy and pharmacology, 2016, 77(3): 623-628.
[5] Isozaki H, Ichihara E, Takigawa N, et al. Non–small cell lung cancer cells acquire resistance to the ALK inhibitor alectinib by activating alternative receptor tyrosine kinases[J]. Cancer research, 2016, 76(6): 1506-1516.
[6] Alam M W, Borenäs M, Lind D E, et al. Alectinib, an anaplastic lymphoma kinase inhibitor, abolishes ALK activity and growth in ALK-positive neuroblastoma cells[J]. Frontiers in oncology, 2019, 9: 579.
[7] Kawauchi D, Takahashi M, Satomi K, et al. The ALK inhibitors, alectinib and ceritinib, induce ALK‐independent and STAT3‐dependent glioblastoma cell death[J]. Cancer Science, 2021, 112(6): 2442-2453.
[8] Hu Y, Chang L, Zhu Y, et al. Inhibition of anaplastic lymphoma kinase protects from ischemic stroke[J]. Stroke, 2024, 55(4): 1075-1085.
[9] Ando C, Ichihara E, Nishi T, et al. Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK‐rearranged non‐small cell lung cancer[J]. Cancer Science, 2023, 114(11): 4343-4354.
Alectinib Hydrochloride是一种强效、选择性、可口服的ALK抑制剂，IC50值为1.9nM，Kd值为2.4nM[1]。Alectinib Hydrochloride可抑制L1196M突变的ALK，IC50值为1.56nM[2]。在过度表达ABCB1或ABCG2的细胞中，Alectinib Hydrochloride通过抑制转运蛋白的外排功能，增加阿霉素（DOX）和罗丹明123（Rho 123）等ABCB1/ABCG2底物的细胞内积累，并刺激ATP酶活性，同时与ABCB1或ABCG2的底物竞争[3]。Alectinib Hydrochloride已被广泛用于抑制具有ALK突变的肺癌细胞的生长[4]。
在体外，Alectinib Hydrochloride处理48小时显著抑制了H2228细胞和ABC-11细胞的增殖，IC50值分别为0.03µM和0.13µM[5]。使用30nM的Alectinib Hydrochloride处理48小时，显著抑制了PC12细胞中ALK介导的神经突生长[6]。使用10µM的Alectinib Hydrochloride处理48小时，诱导了U87MG细胞凋亡，抑制了STAT3的酪氨酸磷酸化，并激活了Janus激酶2（JAK2）的酪氨酸磷酸化[7]。
在体内，单次腹腔注射50mg/kg剂量的Alectinib Hydrochloride 24小时，显著减轻了缺血性卒中小鼠模型中的脑梗死和神经功能缺损，以及脑血管完整性的丧失和血脑屏障的损伤[8]。每日口服10mg/kg剂量的Alectinib Hydrochloride，持续4周，显著抑制了H3122细胞异种移植小鼠模型中的肿瘤生长，且未影响小鼠的体重[9]。
| Cell experiment [1]: | |
Cell lines | U87MG cells |
Preparation Method | U87MG cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and penicillin-streptomycin (1%) at 37°C in a humidified atmosphere containing 5% CO2. The cells were cultured in 96-well plates overnight and incubated with various concentrations of Alectinib Hydrochloride (0, 1, 2, 5, and 10μM) for 48 hours and analyzed for viability. |
Reaction Conditions | 0, 1, 2, 5, and 10μM; 48h |
Applications | Alectinib Hydrochloride treatment decreased the cell viability of U87MG cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female BALB/c nude mice |
Preparation Method | Female BALB/c nude mice (6 weeks old) were fed with sterilized food and water and housed in a barrier facility. The light/dark cycle was 12 hours. H3122 cells (5×106) were injected bilaterally subcutaneously into the mice's backs. The vectors and Alectinib Hydrochloride (10mg/kg) were administered by gavage, once a day, five times a week. The tumor volume was measured twice a week, and the calculation formula was: width2×length/2, for a duration of 4 weeks. |
Dosage form | 10mg/kg/day for 4 weeks; p.o. |
Applications | Alectinib Hydrochloride treatment suppressed tumor growth in the H3122 cell xenograft mouse model without affecting body weight. |
References: | |
| Cas No. | 1256589-74-8 | SDF | |
| 别名 | 艾乐替尼盐酸盐; CH5424802 Hydrochloride; RO5424802 Hydrochloride; AF-802 Hydrochloride | ||
| Canonical SMILES | [H]Cl.N#CC1=CC2=C(C3=C(N2)C(C)(C4=CC(N5CCC(CC5)N6CCOCC6)=C(C=C4C3=O)CC)C)C=C1 | ||
| 分子式 | C30H35ClN4O2 | 分子量 | 519.08 |
| 溶解度 | DMSO: 6 mg/mL (11.56 mM and warming) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9265 mL | 9.6324 mL | 19.2649 mL |
| 5 mM | 385.3 μL | 1.9265 mL | 3.853 mL |
| 10 mM | 192.6 μL | 963.2 μL | 1.9265 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet