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AZM475271
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AZM475271图片
CAS NO:476159-98-5
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 442.94
Formula C23H27ClN4O3
CAS No. 476159-98-5
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:≥ 42 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo) CN1CCC(COC2=CC3=NC=NC(NC4=CC(OC)=CC=C4Cl)=C3C=C2OC)CC1
Synonyms AZM475271; AZM-475271; AZM 475271; M 475271; M475271; M-475271
实验参考方法
In Vitro

In vitro activity: AZM475271 is a potent, selective and oral inhibitor of Src kinase with IC50 of 5 nM and with potential anticancer activities; it has no inhibitory activity on Flt3, KDR, Tie-2. It demonstrated strong dose-dependent inhibition of Src tyrosine kinase activity in the L3.6pl human pancreatic carcinoma cell line. Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Maximum reduction of Src kinase activity was observed after incubation for 4 hours with ≥5 μmol/L. The IC50 concentration of AZM475271 to inhibit the phosphorylation of c-src, lck, and c-yes was 0.01, 0.03, and 0.08 μmol/L, respectively, in comparison with an IC50 of 0.7 μmol/L AZM475271 to inhibit KDR.


Kinase Assay: L3.6pl cells were plated into 10-mm dishes. After overnight incubation, the cells were treated for 4 hours with AZM475271 (1–10 μmol/L). After washing cells with ice-cold PBS, lysates were collected using lysis buffer [50 mmol/L HEPES (pH 7.2), 150 mmol/L NaCl, 1 mmol/L EGTA, 20 mmol/L NAF, 1% Triton X-100, 10% glycerol, 1 mmol/L β-glycerophosphate, 1 mmol/L phenylmethylsulfonyl fluoride, and 1 mmol/L Na3VO4] complemented with protease inhibitor mixture tablets (Roche Diagnostics, Mannheim, Germany). After centrifugation for 10 minutes at 9,000 × g, the supernatant was incubated at 4°C for 4 hours with 15 μg of v-src (Ab-1) monoclonal antibody (Oncogene Research Products, San Diego, CA) preadsorbed to protein A- and protein G-Sepharose (Sigma, Munich, Germany). The immune complex was washed three times with lysis buffer and two times with kinase buffer A [30 mmol/L HEPES (pH 7.5), 5 mmol/L MnCl2, 2 mmol/L dithiothreitol, and 0.1 mmol/L Na3VO4]. Beads were finally resuspended in 4 μL of 5× kinase buffer containing 5 μg of enolase (Sigma) and 10 μCi of [γ-33P]ATP (Perkin-Elmer, Wellesley, MA). After incubation at 30°C for 10 minutes, assays were terminated by the addition of 20 μL of 2× Laemmli sample buffer. The samples were heated at 95°C for 5 minutes and analyzed by SDS-12% PAGE. The gels were dried and subjected to autoradiography. Densitometry of the gels was performed by Gel-Pro Analyzer (Media Cybernetics, Silver Spring, MD).


Cell Assay: AZM475271 demonstrated strong dose-dependent inhibition of Src tyrosine kinase activity in the L3.6pl human pancreatic carcinoma cell line. Maximum reduction of Src kinase activity was observed after incubation for 4 hours with ≥5 μmol/L. The IC50 concentration of AZM475271 to inhibit the phosphorylation of c-src, lck, and c-yes was 0.01, 0.03, and 0.08 μmol/L, respectively, in comparison with an IC50 of 0.7 μmol/L AZM475271 to inhibit KDR

In VivoTumors appeared to be palpable at day 14 after tumor cell injection in all animals except mice treated with both AZM475271 and gemcitabine, in which the earliest possible palpation of the tumors was at day 17 after tumor cell injection. Treatment with gemcitabine or AZM475271 alone did not significantly change animal weight
Animal model Mice
Formulation & Dosage
References J Med Chem. 2004 Feb 12;47(4):871-87.Clin Cancer Res. 2004 Dec 1;10(23):8028-36.