艾樂替尼作用機制 - Medchemexpress - MCE中國

1、Product Data SheetAlectinibCat. No.: HY-13011CAS No.: 1256580-46-7分式: CHNO分量: 482.62作靶點: ALK作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 6.2 mg/mL (12.85 mM; Need warming)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgCo

2、ncentration制備儲備液1 mM 2.0720 mL 10.3601 mL 20.7202 mL5 mM 0.4144 mL 2.0720 mL 4.1440 mL10 mM 0.2072 mL 1.0360 mL 2.0720 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配

3、制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.38 mg/mL (0.79 mM); Clear solution此案可獲得 0.38 mg/mL (0.79 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 3.8 mg/mL

4、 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.38 mg/mL (0.79 mM); Precipitated solution; Need ultrasonicPage 1 of 2 www.MedChemE此案可獲得 0.38 mg/mL (0.79 mM)以 1 mL 作液為例，取 100 L 3.8 mg/mL 的澄均勻。DMSO 儲備液加到

5、900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.38 mg/mL (0.79 mM); Clear solution此案可獲得 0.38 mg/mL (0.79 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 3.8 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Alectinib (CH5424802; RO5424802; AF802)種有效，選擇性和服的 A

6、LK 抑制劑，其 IC50 為 1.9 nM，Kd 值為 2.4nM (以 ATP 競爭式)，并且還抑制 ALK F1174L 和 ALK R1275Q，其 IC50 分別為 1 nM 和 3.5 nM。Alectinib 還具有有效的中樞神經(jīng)系統(tǒng) (CNS) 滲透能。IC & Target IC50: 1.9 nM(ALK), 1 nM (ALKF1174L), 3.5 nM (ALKR1275Q)1Kd: 2.4 nM (ALK)1體外研究 Alectinib (0-1000 nM; 2 hours; NCI-H2228 cells) treatment could prevent aut

7、ophosphorylation of ALK in NCI-H2228cells expressing EML4-ALK, and it also resulted in substantial suppression of phosphorylation of STAT3 and AKT1.Alectinib (0-1000 nM; 5 days; HCC827, A549, or NCIH522 cells) treatment reduces cell activity in a dose-dependentmanner1.Western Blot Analysis1Cell Line

8、: NCI-H2228 cellsConcentration: 0 nM,10 nM,100 nM, 1000 nMIncubation Time: 2 hoursResult: Inhibition of ALK phosphorylation and signal transduction.Cell Viability Assay1Cell Line: HCC827, A549, or NCIH522 cellsConcentration: 0-1000 nMIncubation Time: 5 daysResult: Reduced cell activity in a dose-dep

9、endent manner.體內(nèi)研究Alectinib (0.2-20 mg/kg; oral administration; once daily; for 11 days; SCID or nude mice bearing NCI-H2228 cells)dose level, no differences in body weight or gross signs of toxicity are observed1.treatment can result in dose-dependent tumor growth inhibition (EC50 of 0.46 mg/kg) an

10、d tumor regression. At anyAnimal Model: SCID or nude mice bearing NCI-H2228 cells1Dosage: 0.2 mg/kg, 0.6 mg/kg, 2 mg/kg, 6 mg/kg, 20 mg/kgAdministration: Oral administration; once daily; for 11 daysPage 2 of 3 www.MedChemEResult: Resulted in dose-dependent tumor growth inhibition (EC50 of 0.46 mg/kg

11、) and tumorregression.戶使本產(chǎn)品發(fā)表的科研獻 Science. 2017 Dec 1;358(6367). pii: eaan4368. Science. 2014 Oct 3;346(6205):1255784. Cancer Discov. 2018 Jun;8(6):714-729. Cancer Discov. 2016 Oct;6(10):1118-1133. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK www.MedC

12、hemE www.MedChemEREFERENCES1. Sakamoto H, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011, 19(5), 679-690.2. Gadgeel S, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacyresults from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222.McePdfHeightCaution: Product has not