塞卡替尼作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetSaracatinibCat. No.: HY-10234CAS No.: 379231-04-6分式: CHClNO分量: 542.03作靶點(diǎn): Src; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy儲(chǔ)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(shí)驗(yàn) DMSO : 32 mg/mL (59.04 mM)* means soluble, but saturation unknown.Solve

2、ntMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 1.8449 mL 9.2246 mL 18.4492 mL5 mM 0.3690 mL 1.8449 mL 3.6898 mL10 mM 0.1845 mL 0.9225 mL 1.8449 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮?/p>

3、以下溶解案都請(qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.61 mM); Clear solution此案可獲得 2.5 mg/mL (4.61 mM，飽和度未知) 的澄清溶液。以 1 mL 作液

4、為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.61 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (4.61 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄

5、 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Saracatinib (AZD0530) nM 。種有效的 Src 抑制劑，抑制 c-Src，Lck，c-YES，Lyn，F(xiàn)yn，F(xiàn)gr 和 Blk, IC50 為 2.7 11IC & Target IC50: 2.7 nM (Src), 30 nM (v-Abl), 66 nM (EGFR), 200 nM (c-Kit)1體外研究 Saracatinib (AZD0530), an orally available Src inhibitor, demonstrates potent an

6、timigratory and anti-invasive effects invitro, and inhibits metastasis in a murine model of bladder cancer. Antiproliferative activity of Saracatinib variesbetween cell lines (IC50 0.2-10 M). Saracatinib potently inhibits the proliferation of Src3T3 mouse fibroblasts anddemonstrates variable antipro

7、liferative activity in a range of human cancer cell lines containing endogenous Src. Submicromolar growth inhibition of five of the human cancer cell lines tested with Saracatinib (tumor types: colon,prostate, lung, and leukemia) is observed with IC50 values of 0.2-0.7 M. In 3-day MTS cell prolifera

8、tion assays,Saracatinib inhibits proliferation of the Bcr-Abl-driven human leukemia cell line K562 with an IC50 of 0.22 M. In themicrodroplet migration assay, Saracatinib reduces the migration of human lung cancer A549 cells in a concentration-dependent manner (IC50 0.14 M)1.體內(nèi)研究 Saracatinib (AZD053

9、0) treatment potently inhibits the proliferation of subcutaneously transplanted Src3T3 fibroblastsin mice and rats in a dose-dependent manner. In both models, significant inhibition of tumor growth is seen at doses6 mg/kg/day (60% inhibition in mice and 98% inhibition in rats versus animals treated

10、with vehicle) and, at themaximum doses investigated, complete tumor growth inhibition is observed (100% inhibition at 25 mg/kg/day inmice and 10 mg/kg/day in rats)1.PROTOCOLKinase Assay 1 Investigation of the reversibility and the mechanism of Saracatinib inhibition is conducted using a full-lengtha

11、ctivated human Src in a continuous, coupled assay. ATP and peptide substrate (Src II peptide) concentrations arevaried in turn (ATP 40-1280 M; Src II peptide 100-800 M), in conjunction with Saracatinib (0-30 nM), at saturatingconcentrations of the non-varied substrate (ATP 1.6 mM; Src II peptide 1.0

12、 mM). The binding affinity of Saracatinibfor inactivated Src (phosphorylated at tyrosine 527, not tyrosine 416) is measured using a BIAcore inhibition-in-solution assay. The assay followed competition binding between Saracatinib and an immobilized ureidoquinazolinefor binding to Src. Data analysis i

13、s performed by unweighted nonlinear regression using GraFit, version 5 and an F-test is used to identify the most suitable equation1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cell proliferation is assessed using a colorimetric 5-bromo

14、-2-deoxyuridine (BrdU) Cell Proliferation ELISA kit. Briefly,cells are plated onto 96-well plates (1.5104 cells/well), the following day 0.039-20 M Saracatinib in DMSO (at afinal concentration of 0.5%) is added and the cells are incubated for 24 h. The cells are pulse labeled with BrdU for 2h and fi

15、xed. Cellular DNA is then denatured with the provided solution and incubated with antiBrdU peroxidase for90 min. Following three washes with phosphate-buffered saline, tetramethylbenzidine substrate solution is addedand the plates are incubated on a plate shaker for 10-30 min until the positive cont

16、rol absorbance at 690 nm isapproximately 1.5 absorbance units1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemEAnimal Mice and Rats1Administration 1 Female athymic mice (nu/nu) and rats (RH-rnu/rnu) are used. Animals are treated

17、once daily by oral gavage witheither vehicle alone or Saracatinib 6.25-50 mg/kg for 10-91 days. Tumor growth inhibition is calculated. Forpharmacokinetic and pharmacodynamic analysis animals are humanely sacrificed and samples (plasma and tumor)are collected. Tumor samples are homogenized with 5 vol

18、umes of water and extracted with chloroform. Plasma andtumor samples are analyzed for Saracatinib concentration using high-performance liquid chromatography withtandem mass spectrometric detection after solid-phase extraction.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Leukemia. 2012 Oct;26(10):2233-44. Mol Cancer Ther. 2017 Nov;16(11):2387-2398. Cancer Sci. 2018 Jun;109(6):1949-1957. J Cell Mol Med. 2019 Apr;23(4):2399-2409.See more customer validations on HYPERLINK www