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| 25mg |
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Purity: ≥98%
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 showed a significant dose-dependent reduction in the activity of Src tyrosine kinase in the human pancreatic cancer cell line L3.6pl. It is thought that aberrant activity of the nonreceptor tyrosine kinase c-Src leads to alterations in adhesion, cytoskeleton, and signal transduction, all of which eventually encourage a tumor-invasive phenotype. inhibitors that have a strong affinity and specificity for the c-Src enzyme's tyrosine kinase domain. The highest decrease in Src kinase activity was noted following a 4-hour incubation period at ≥5 μmol/L. Compared to an IC50 of 0.7 μmol/L for AZM475271 to inhibit KDR, the IC50 concentration of AZM475271 to inhibit the phosphorylation of c-src, lck, and c-yes was 0.01 μmol/L, 0.03 μmol/L, and 0.03 μmol/L, respectively.
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| ln Vivo |
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| Enzyme Assay |
Plates measuring 10 mm were filled with L3.6pl cells. Following an overnight incubation period, AZM475271 (1–10 μmol/L) was applied to the cells for 4 hours. Lysates were obtained 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] supplemented with tablets of a protease inhibitor mixture (Roche Diagnostics, Mannheim, Germany). Following 10 minutes of 9,000 ×g centrifugation, 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) were incubated at 4°C for 4 hours. The immunological complex was rinsed twice with kinase buffer A and three times with lysis buffer [0.1 mmol/L Na3VO4, 5 mmol/L MnCl2, 2 mmol/L dithiothreitol, and 30 mmol/L HEPES (pH 7.5)]. At last, the beads were reconstituted in 4 μL of 5× kinase buffer, which contained 10 μCi of [γ-33P]ATP (Perkin-Elmer, Wellesley, MA) along with 5 μg of enolase (available from Sigma). Assays were stopped by adding 20 μL of 2× Laemmli sample buffer after they had been incubated at 30°C for 10 minutes. After five minutes of heating at 95°C, the samples were subjected to SDS-12% PAGE analysis. After drying, the gels were autoradiographically examined. The Gel-Pro Analyzer (Media Cybernetics, Silver Spring, MD) was used to measure the densitometry of the gels.
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| Cell Assay |
The L3.6pl human pancreatic carcinoma cell line showed significant dose-dependent inhibition of Src tyrosine kinase activity in response to AZM475271. The highest decrease in Src kinase activity was noted following a 4-hour incubation period at ≥5 μmol/L. Compared to AZM475271's 0.7 μmol/L IC50 to inhibit KDR, the phosphorylation of c-src, lck, and c-yes was inhibited at IC50 values of 0.01–0.03, 0.03– and 0.08 μmol/L, respectively.
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| Animal Protocol |
Mice
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| References |
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| Additional Infomation |
Src Kinase Inhibitor M475271 is an inhibitor of Src tyrosine kinase, with potential antineoplastic activity. Upon administration, Src kinase inhibitor M-475271 targets and binds to Src kinase. This inhibits Src-mediated signaling and the proliferation of tumor cells overexpressing Src. Src tyrosine kinase, a non-receptor tyrosine kinase upregulated in many tumor cell types, plays an important role in tumor cell proliferation, motility, invasiveness and survival.
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| Molecular Formula |
C23H27CLN4O3
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| Molecular Weight |
442.94
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| Exact Mass |
442.177
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| Elemental Analysis |
C, 62.37; H, 6.14; Cl, 8.00; N, 12.65; O, 10.84
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| CAS # |
476159-98-5
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| Related CAS # |
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| PubChem CID |
5330175
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| Appearance |
White to off-white solid powder
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| LogP |
4.775
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
551
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCC(COC2=CC3=NC=NC(NC4=CC(OC)=CC=C4Cl)=C3C=C2OC)CC1
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| InChi Key |
WPOXAFXHRJYEIC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27ClN4O3/c1-28-8-6-15(7-9-28)13-31-22-12-19-17(11-21(22)30-3)23(26-14-25-19)27-20-10-16(29-2)4-5-18(20)24/h4-5,10-12,14-15H,6-9,13H2,1-3H3,(H,25,26,27)
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| Chemical Name |
N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2576 mL | 11.2882 mL | 22.5764 mL | |
| 5 mM | 0.4515 mL | 2.2576 mL | 4.5153 mL | |
| 10 mM | 0.2258 mL | 1.1288 mL | 2.2576 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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