Saracatinib (AZD0530)
Saracatinib (AZD0530) is a novel, potent Src family kinase (SFK)/Abl dual-kinase inhibitor with IC50 value of 2.7 nM [1].
Saracatinib has been reported to inhibit Src activation in DU145 and PC3 cell lines (prostate cancer cell lines). Both of c-Myc and cyclin D1 expression are decreased by Saracatinib. Saracatinib can inhibit the ERK1/2 and GSK3b phosphorylation as well as decrease β-catenin level in cells. Saracatinib inhibits the prostate tumor cell growth by inducing cycle arrest at G1/S phase. Saracatinib dose-dependently blocks cell migration in DU145 and PC3 cell lines [1].
In DU145 implanted orthotopic SCID mice model, treatment with Saracatinib has been demonstrated to down-regulate the Src expression as well as suppress the tumor size [1].
References:
[1] Chang YM1, Bai L, Liu S, Yang JC, Kung HJ, Evans CP. Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530. Oncogene. 2008 Oct 23;27(49):6365-75.
- 1. Andrew Dimond, Do Hyeon Gim, et al. "PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites." bioRxiv. April 23, 2024.
- 2. Xu Wang, Xinfang Yu, et al. "Expanding anti-CD38 immunotherapy for lymphoid malignancies." J Exp Clin Cancer Res. 2022 Jun 28;41(1):210 PMID: 35765110
- 3. Christopher M Dustin, Aida Habibovic, et al. "Oxidation–Dependent Activation of Src Kinase Mediates Epithelial IL-33 Production and Signaling during Acute Airway Allergen Challenge." J Immunol. 2021 Jun 15;206(12):2989-2999. PMID: 34088769
- 4. Liao X, Song G, et al. "Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma." BMC Cancer. 2020;20(1):31. PMID: 31931755
- 5. Panagi I, Jennings E, et al. "Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization." Cell Host Microbe. 2020;27(1):41–53.e6. PMID: 31862381
- 6. Alzubi MA, Turner TH, et al. "Separation of breast cancer and organ microenvironment transcriptomes in metastases." Breast Cancer Res. 2019 Mar 6;21(1):36. PMID: 30841919
- 7. Nakachi I, Helfrich BA, et al. "PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines." Clin Transl Sci. 2016 Dec;9(6):293-301. PMID: 27766744
- 8. Diao Y, Ma X, et al. "Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src." Cancer Lett. 2016 May 16. PMID: 27195913
| Storage | Store at -20°C |
| M.Wt | 542.03 |
| Cas No. | 379231-04-6 |
| Formula | C27H32ClN5O5 |
| Solubility | ≥27.1 mg/mL in DMSO; insoluble in EtOH; ≥2.36 mg/mL in H2O with ultrasonic |
| Chemical Name | N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine |
| SDF | Download SDF |
| Canonical SMILES | CN1CCN(CC1)CCOC2=CC(=C3C(=C2)N=CN=C3NC4=C(C=CC5=C4OCO5)Cl)OC6CCOCC6 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
A549 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 24 hours for cell migration inhibition 48 hours for cell invasion inhibition |
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Applications |
A549 cells were grown to confluent monolayers, which were scratched with a pipette tip and incubated with AZD0530 at concentrations ranging from 100 to 1000 nM. DMSO treated control cells continuously migrated into the scratch and nearly closed the scratch within 24 hours. Cell migration was significantly inhibited by AZD0530 in a dose-dependent way. At the highest dose tested (1 μM), AZD0530 reduced A549 cell migration by more than 60%. Cell invasion was tested using a modified Matrigel assay with A549 cells. AZD0530 significantly reduced Matrigel invasion in A549 cells by 51%. |
| Animal experiment: [2] | |
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Animal models |
Female athymic nude mice injected with Panc410 cells |
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Dosage form |
Oral administration, 50mg/kg/d for 28 days |
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Applications |
AZD0530 administration clearly down-regulated Src, FAK, p-FAK, and pSTAT-3 expression in the sensitive tumor (Panc410) compared with control tumors. In addition, AZD0530 administration resulted in the down-regulation of XIAP as evidenced by the immunoblot of Panc410. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Purnell P R, Mack P C, Tepper C G, et al. The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 2009, 4(4): 448. [2] Rajeshkumar N V, Tan A C, De Oliveira E, et al. Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer. Clinical Cancer Research, 2009, 15(12): 4138-4146. |
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| Description | Saracatinib (AZD0530) is a potent inhibitor of Src 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). | |||||
| Targets | c-Src | v-Abl | ||||
| IC50 | 2.7 nM | 30 nM | ||||
Quality Control & MSDS
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