Antibodies
Saracatinib (AZD0530)
- 貨號 Cat. No.
- S1006
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Saracatinib (AZD0530)
Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). Phase 1/2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). Phase 1/2. | |||||
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| Targets | c-Src | v-Abl | ||||
| IC50 | 2.7 nM | 30 nM [1] | ||||
| In vitro | Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. Saracatinib sensitively inhibits Src Y530F NIH 3T3 with IC50 of 80 nM. Saracatinib signiï¬cantly impairs the invasion of HT1080 cells through a 3-dimensional collagen matrix and completely inhibits EGF-induced cell scattering in NBT-II bladder cancer cells. [1] Saracatinib potent inhibits Src activation in DU145 and PC3 cells, which through inhibition of Y419 phosphorylation. Saracatinib inhibits the growth of prostate cancer including PC3, DU145, CWR22Rv1 and LNCaP, while Saracatinib shows low activity in LAPC-4, PZ-HPV7 and RWPE-1 cells. Saracatinib induces cell cycle arrest at G1/S but not caspase 3 cleavages. Saracatinib also significantly inhibits DU145 and PC3 migration in the Boyden chamber. [2]Saracatinib gives a potent and sustained blockage of AKT and enhances the sensitivity to irradiation in A549 and Calu-6 cells. [3] Saracatinib inhibits osteoclast in activity, resorption and formation. Saracatinib also reversibly prevents osteoclast precursor migration. [4] | |||||
| In vivo | Saracatinib shows great tumor growth inhibition in Src3T3 allografts and a moderate growth delay in Calu-6, MDA-MB-231, AsPc-1 and BT474C xenografts. [1] Saracatinib shows great antitumor activity in orthotopic DU145 xenograft mice at a dose of 25mg/kg (orally administered, daily). [2] | |||||
| Features | The 1st Src inhibitor to show inhibition of the Src pathway in human tumor tissue. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Kinase Assay | IC50 of tyrosine kinase activity is measured by an enzyme-linked immunosorbent assay (ELISA) with recombinant catalytic domains of a panel of receptor and non-receptor tyrosine kinases (in some cases only part of the catalytic domain is used). Saracatinib dose ranges from 0.001-10 mM. Speciï¬city assays against a panel of serine/threonine kinases are performed using a ï¬lter capture assay with 32P. Briefly, multidrop 384 plates containing 0.5 μL Saracatinib or controls (DMSO) alone or pH 3.0 buffer controls) are incubated with 15 μL of enzyme plus peptide/protein substrate for 5 min before the reaction is initiated by the addition of 10 μL of 20 mM Mg-ATP. For all enzymes the ï¬nal concentration is approximated to the Michaelis constant (Km). Assays are carried out for 30min at room temperature before termination by the addition of 5 μL orthophosphoric acid. After mixing, the well contents are harvested onto a P81 Uniï¬lter plate, using orthophosphoric acid as the wash buffer. Then IC50 is calculated. |
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Cell Assay: [1]
| Cell lines | PC3, DU145, CWR22Rv1, LNCaP, LAPC-4, PZ-HPV7 and RWPE-1 cells |
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| Concentrations | 62.5 nM - 16 mM |
| Incubation Time | 1, 3 and 5 days |
| Method | Cells are seeded at a density of 2× 103 in 96-well plates and incubated overnight. Then Saracatinib (62.5 nM-16 mM) is added to the cells. After 1, 3 and 5 days, culture medium is removed followed by addition of 0.2 mL DMSO per well and continuous shaking of plates at 200 rotations per minute for 15min. Then IC50 is measured by MTT metho |
Animal Study: [1]
| Animal Models | CB17 mice are implanted with DU145 cells. |
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| Dosages | 25 mg/kg |
| Administration | Orally administered daily |
| Solubility | 0.5% methylcellulose/0.2% Tween 80, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00752206 | Recruiting | Osteosarcoma | Sarcoma Alliance for Research through Collaboration|AstraZeneca | 2009-03 | Phase 2 |
| NCT00853983 | Completed | Healthy | AstraZeneca | 2009-03 | Phase 1 |
| NCT01000896 | Withdrawn | Cancer|Non Small Cell Lung Cancer|Epithelial Ovarian Cancer | AstraZeneca | 2010-01 | Phase 1 |
| NCT01267266 | Active, not recruiting | Hormone-resistant Prostate Cancer|Recurrent Prostate Cancer|Stage IV Prostate Cancer | National Cancer Institute (NCI) | 2010-12 | Phase 2 |
| NCT01864655 | Not yet recruiting | Alzheimer’s Disease | Yale University|Stephen M. Strittmatter | 2013-07 | Phase 1 |
Chemical Information
Download Saracatinib (AZD0530) SDF
| Molecular Weight (MW) | 542.03 |
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| Formula | C27H32ClN5O5 |
| CAS No. | 379231-04-6 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (184 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 100 mg/mL (184 mM) | ||
| In vivo | 0.5% methylcellulose/0.2% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | N-(5-chlorobenzo[d][1,3]dioxol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.54203 | 5.4203 | 10.8406 | 16.2609 |
Customer Reviews (8)
 Click to enlarge | Rating | |
| Source | Cancer Res, 2011, 71(24), 7547-57. Saracatinib (AZD0530) purchased from Selleck | |
| Method | Tumor xenograft experiments | |
| Cell Lines | tumor xenografted nude mice | |
| Concentrations | 25 mg/kg | |
| Incubation Time | 4 weeks | |
| Results | tumor xenograft experiments in nude mice showed that orally saracatinib administration could also alleviate instigative tumor formation induced by stable LHBs expression in Huh7 and SK-Hep1 cells . |
Product Citations (14)
F- and G-actin homeostasis regulates mechanosensitive actin nucleation by formins. [Higashida C, et al. Nat Cell Biol 2013;15(4):395-405]
Hepatitis B virus large surface antigen promotes liver carcinogenesis by activating the Src/PI3K/Akt pathway. [Liu H, et al. Cancer Res 2011;71(24):7547-57]
Saracatinib (AZD0530) is a potent modulator of ABCB1-mediated multidrug resistance in vitro and in vivo. [Liu KJ, et al. Int J Cancer 2013;132(1):224-35]
