1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESaracatinibCat. No.: HY-10234CAS No.: 379231-04-6Synonyms: AZD0530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)

2、DMSO : 32 mg/mL (59.04 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration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，并請(qǐng)注意儲(chǔ)備液的保存式和期限。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?，配制前?qǐng)先配制澄清的儲(chǔ)備液

3、，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：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 solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.61 mM); Clear solution1/3 Master of Small Molecul

4、es 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Saracatinib (AZD0530)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 11 nM 。IC50 & 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 anti

5、migratory and anti-invasiveeffects in vitro, and inhibits metastasis in a murine model of bladder cancer. Antiproliferative activity ofSaracatinib varies between cell lines (IC50 0.2-10 M). Saracatinib potently inhibits the proliferation ofSrc3T3 mouse fibroblasts and demonstrates variable antiproli

6、ferative activity in a range of human cancer celllines containing endogenous Src. Sub micromolar growth inhibition of five of the human cancer cell linestested with Saracatinib (tumor types: colon, prostate, lung, and leukemia) is observed with IC50 values of0.2-0.7 M. In 3-day MTS cell proliferatio

7、n assays, Saracatinib inhibits proliferation of the Bcr-Abl-drivenhuman leukemia cell line K562 with an IC50 of 0.22 M. In the microdroplet migration assay, Saracatinibreduces the migration of human lung cancer A549 cells in a concentration-dependent manner (IC50 0.14 M)1.體內(nèi)研究 Saracatinib (AZD0530)

8、treatment potently inhibits the proliferation of subcutaneously transplanted Src3T3fibroblasts in mice and rats in a dose-dependent manner. In both models, significant inhibition of tumorgrowth is seen at doses 6 mg/kg/day (60% inhibition in mice and 98% inhibition in rats versus animalstreated with

9、 vehicle) and, at the maximum doses investigated, complete tumor growth inhibition is observed(100% inhibition at 25 mg/kg/day in mice 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-lengthact

10、ivated human Src in a continuous, coupled assay. ATP and peptide substrate (Src II peptide)concentrations are varied in turn (ATP 40-1280 M; Src II peptide 100-800 M), in conjunction withSaracatinib (0-30 nM), at saturating concentrations of the non-varied substrate (ATP 1.6 mM; Src II peptide1.0 mM

11、). The binding affinity of Saracatinib for inactivated Src (phosphorylated at tyrosine 527, not tyrosine416) is measured using a BIAcore inhibition-in-solution assay. The assay followed competition bindingbetween Saracatinib and an immobilized ureidoquinazoline for binding to Src. Data analysis is p

12、erformed byunweighted nonlinear regression using GraFit, version 5 and an F-test is used to identify the most suitableequation 1.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-2-d

13、eoxyuridine (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 inDMSO (at a final concentration of 0.5%) is added and the cells are incubated for 24 h. The cells are pulselabeled with BrdU for 2 h and fixed.

14、 Cellular DNA is then denatured with the provided solution and incubatedwith antiBrdU peroxidase for 90 min. Following three washes with phosphate-buffered saline,2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEtetramethylbenzidine substrate solution is added and the plates are incubated on a plate

15、 shaker for 10-30min until the positive control absorbance at 690 nm is approximately 1.5 absorbance units 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice and Rats 1Administration 1 Female athymic mice (nu/nu) and rats (RH-rnu/rnu) are use

16、d. Animals are treated once daily by oral gavagewith either vehicle alone or Saracatinib 6.25-50 mg/kg for 10-91 days. Tumor growth inhibition is calculated.For pharmacokinetic and pharmacodynamic analysis animals are humanely sacrificed and samples (plasmaand tumor) are collected. Tumor samples are

17、 homogenized with 5 volumes of water and extracted withchloroform. Plasma and tumor samples are analyzed for Saracatinib concentration using high-performanceliquid chromatography with tandem mass spectrometric detection after solid-phase extraction.MCE has not independently confirmed the accuracy of

18、 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 /