|
受注：045-509-1970 |
技術サポート：[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
|
Synonyms | AF-802, RG-7853,CH5424802 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C30H34N4O2 |
|||
| 分子量 | 482.62 | CAS No. | 1256580-46-7 | |
| Solubility (25°C)* | 体外 | 4-Methylpyridine | 21 mg/mL (43.51 mM) | |
| DMSO | 1 mg/mL warmed with 50ºC water bath (2.07 mM) | |||
| Water | Insoluble | |||
|
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
||||
溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Alectinib is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429. |
|---|---|
| in vitro | The dissociation constant (KD) value of CH5424802 for ALK in an ATP-competitive manner is 2.4 nM. CH5424802 has substantial inhibitory potency against both native ALK and L1196M with Ki of 0.83 nM and 1.56 nM, respectively. CH5424802 prevents autophosphorylation of ALK in NCI-H2228 NSCLC cells expressing EML4-ALK. CH5424802 also suppresses the phosphorylation of STAT3 and AKT, but not of ERK1/2. CH5424802 completely inhibits the phosphorylation of STAT3 at Tyr705. CH5424802 is preferentially efficacious against NCI-H2228 cells expressing EML4-ALK, but not ALK fusion-negative NSCLC cell lines, including HCC827 cells (EGFR exon 19 deletion), A549 cells (KRAS mutant), or NCI-H522 cells (EGFR wild-type, KRAS wild-type, and ALK wild-type) in monolayer culture. CH5424802 elicits an apoptotic marker—caspase-3/7-like activation—in NCI-H2228 spheroid cells. CH5424802 blocks the growth of two lymphoma lines, KARPAS-299 and SR, with NPM-ALK fusion protein but does not influence the growth of an HDLM-2 lymphoma line without ALK fusion. [1] CH5424802 displays high target selectivity and the stronger anti-proliferative activity against KARPAS-299. CH5424802 inhibits KAPRAS-299 with an IC50 of 3 nM, and KDR with IC50 of 1.4 μM. The metabolic stability of CH5424802 is very high.[2] |
| in vivo | Oral administration of CH5424802 dose-dependently inhibits tumor growth with an ED50 of 0.46 mg/kg and tumor regression. Treatment of 20 mg/kg CH5424802 reveals rapid tumor regression by 168%, the tumor volume in any mouse is <30 mm3 after 11 days of treatment (at day 28), a potent antitumor effect is maintained, and tumor regrowth does not occur throughout the 4-week drug-free period. The half-life and the oral bioavailability of CH5424802 in mice are 8.6 hours and 70.8%, respectively. At a repeated dose of 6 mg/kg, the mean plasma levels reached 1.7, 1.5, and 0.3 nM at 2, 7, and 24 hours post-dose, respectively. Administration of CH5424802 leads to tumor growth prevention and tumor regression. Tumor growth inhibition at 20 mg/kg is 119% for KARPAS-299 and 104% for NB-1 on day 20. CH5424802 inhibits the phosphorylation of STAT3 in a dose-dependent manner (2–20 mg/kg). A partial decrease in AKT phosphorylation is also observed in CH5424802-treated xenograft tumors. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Kinase inhibitory assays in Vitro | |
|---|---|---|
| The inhibitory ability against each kinase except for MEK1 and Raf-1 is evaluated by examining their ability to phosphorylate various substrate peptides in the presence of CH5424802 using time-resolved fluorescence resonance energy transfer (TR-FRET) assay or fluorescence polarization (FP) assay. The inhibitory activity against MEK1 is evaluated by quantitative analysis of the phosphorylation of a substrate peptide by a recombinant ERK2 protein in the presence of CH5424802. The inhibitory activity against Raf-1 is evaluated by examining the ability of the kinases to phosphorylate MEK1 in the presence of CH5424802. | ||
| 細胞アッセイ | 細胞株 | NSCLC, A549 and HCC827 cell lines |
| 濃度 | 0-1 μM | |
| 反応時間 | 5 days | |
| 実験の流れ | Cells including NSCLC, A549 and HCC827 are seeded in 96-well plates overnight and incubated with various concentrations of CH5424802 for the indicated time. For spheroid cell growth inhibition assay, cells are seeded on spheroid plates, incubated overnight, and then treated with compound for the indicated times. The viable cells are measured by the Luminescent Cell Viability Assay. Caspase-3/7 assay is evaluated using the Caspase-Glo 3/7 Assay Kit. | |
| 動物実験 | 動物モデル | SCID or nude mice bearing NCI-H2228 |
| 投薬量 | 20 mg/kg | |
| 投与方法 | Oral administration | |
参考
|
カスタマーフィードバック
-
Data from [Data independently produced by Int J Oncol, 2014, 45(4), 1430-6]
-
, , Prof. Gambacorti from Università degli Studi di Milano Bicocc
-
, , Prof. Gambacorti from Università degli Studi di Milano Bicocc
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations [ Cancer Discov, 2024, OF1-OF20.] | PubMed: 39269178 |
| Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer [ Nat Commun, 2024, 15(1):3741] | PubMed: 38702301 |
| Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions [ Nat Commun, 2024, 15(1):51] | PubMed: 38168093 |
| LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion [ Commun Biol, 2024, 7(1):412] | PubMed: 38575808 |
| Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of β-Cyclodextrin and Hydroxypropyl β-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib [ Pharmaceuticals (Basel), 2024, 17(6)737] | PubMed: 38931404 |
| Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment [ BMC Pharmacol Toxicol, 2024, 25(1):25] | PubMed: 38444002 |
| Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment [ BMC Pharmacol Toxicol, 2024, 25(1):25] | PubMed: 38444002 |
| Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models [ Clin Cancer Res, 2023, 29(7):1317-1331] | PubMed: 36602782 |
| Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms [ Clin Cancer Res, 2023, 29(5):943-956] | PubMed: 36537918 |
| Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma [ Cell Rep, 2023, 42(3):112212] | PubMed: 36870059 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。