Alectinib Hydrochloride |
رقم الكتالوجGC35280
One-Click Copy Product Info
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Alectinib Hydrochloride (CH5424802 Hydrochloride؛ RO5424802 Hydrochloride؛ AF-802 Hydrochloride) هو مثبط ALK فعال وانتقائي ومتوفر عن طريق الفم مع IC50 من 1.9 نانومتر وقيمة Kd 2.4 نانومتر (بطريقة تنافسية ATP) ، ويمنع أيضًا ALK F1174L و ALK R1275Q مع IC50s من 1 نانومتر و 3.5 نانومتر ، على التوالييوضح Alectinib اختراقًا فعالًا للجهاز العصبي المركزي (CNS)
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1256589-74-8
Sample solution is provided at 25 µL, 10mM.
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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.
| 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 | |
| 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 | ||
| Formula | C30H35ClN4O2 | M.Wt | 519.08 |
| الذوبان | DMSO: 6 mg/mL (11.56 mM and warming) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)