AZD4547
Catalog No.S2801
Molecular Weight(MW): 463.57
AZD4547 is a novel selective FGFR inhibitor targeting FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2(KDR), and little activity observed against IGFR, CDK2, and p38. Phase 2/3.
5 Customer Reviews
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Ependymoma cells and neural stem cell line 1 (NSC1) controls treated with or AZD4547 for 72 h and assessed using an Alamar Blue stain. Error bars show s.d. Experiment performed as six technical replicates and replicated in biological triplicates.
Nature, 2018, 553(7686):101-105. AZD4547 purchased from Selleck.
A-431 and ACHN cells that are partially sensitive to the EGFR inhibitor gefitinib were treated with gefitinib, the FGFR inhibitor AZD-4547, or a combination of both. Error bars depict SEM of three experiments. Cell viability and proliferation assays showed that the combination of the drugs was more effective than single compounds.
Science, 2017, doi: 10.1126/science.aan4368. AZD4547 purchased from Selleck.
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(b) Representative pictures of Vim expression in four groups. Bars=20 μm. (c) A box plot graph showing the quantitative evaluation of Vim staining intensity. A plot of a box plot with whiskers extending from the 5th to the 95th percentile of all the score data was used. (d) Representative pictures of Sirius red staining in tumor samples from 32 nude mice. Sirius red staining showed the increased collagen fiber in TGF +AZD group. Bars=100 μm. Percentage of positive area to total area is quantified.
Oncogene, 2017, 36(27):3831-3841. AZD4547 purchased from Selleck.
FCM evaluating lung CD11b+/Gr1+ myeloid cells isolated from 4T1 tumor-bearing mice after 20 days of treatment with AZD4547 or control. Statistical significance was assessed by unpaired t test.
Cell Physiol Biochem 2014 33(3), 633-45. AZD4547 purchased from Selleck.
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Treatment of human CECs with of IL-1β (*, P < 0.01) and FGF2 (+, P < 0.01) resulted in enhanced cell migration as measured in a scratch-induced directional migration assay. Cotreatment with AZD4547 (AZD), an antagonist against FGF receptors 1 to 3, abolished the FGF2-enhanced (++, P < 0.01) but not the IL-1β-enhanced (P > 0.05) migration in human CECs. One-way ANOVA: F(4, 80) = 512, P < 0.00001, n =17 per sample. Tukey's post hoc test, HSD[0.05] = 10.9; HSD[0.01] = 13.1.
Mol Cell Biol 2014 34(18), 3535-45. AZD4547 purchased from Selleck.
Purity & Quality Control
Choose Selective FGFR Inhibitors
Biological Activity
| Description | AZD4547 is a novel selective FGFR inhibitor targeting FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2(KDR), and little activity observed against IGFR, CDK2, and p38. Phase 2/3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Greater selectivity for FGFR1-3 over FGFR4. AZD4547 is active against the tyrosine kinase activity of both the wild-type and mutant forms of FGFR. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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| In vitro |
Compared to FGFR1-3, AZD4547 displays weaker activity against FGFR4 with IC50 of 165 nM. AZD4547 only inhibits recombinant VEGFR2 (KDR) kinase activity with IC50 of 24 nM, in the in vitro selectivity test against a diverse panel of representative human kinases. AZD4547 at 0.1 μM exhibits no activity against a range of recombinant kinases including ALK, CHK1, EGFR, MAPK1, MEK1, p70S6K, PDGFR, PKB, Src, Tie2, and PI3-kinase. Consistently, the potent selectivity of AZD4547 for FGFR1-3 over FGFR4, IGFR, and KDR is also observed in cellular phosphorylation assays. AZD4547 has potent in vitro antiproliferative activity only against tumor cell lines expressing deregulated FGFRs such as KG1a, Sum52-PE, and KMS11 with IC50 of 18-281 nM, and is inactive against MCF7 as well as more than 100 additional tumor cell lines. AZD4547 treatment potently inhibits FGFR and MAPK phosphorylation in human tumor cell lines in a dose-dependent manner. AZD4547 also potently inhibits the phosphorylation of FRS2 and PLCγ, downstream markers of FGFR signaling. Notably, AZD4547 affects the AKT phosphorylation in the breast cell lines, MCF7 and Sum52-PE but not in KG1a and KMS11 lines. AZD4547 treatment significantly induces apoptosis in Sum52-PE and KMS11 cells, dramatically increases G1 arrest but not apoptosis in KG1a cells, and has no effect on cell cycle distribution or apoptosis in MCF7 cells. [1] |
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| Cell Data |
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| In vivo | Oral administration of AZD4547 at 3 mg/kg twice daily in mice bearing KMS11 tumors results in significant tumor growth inhibition of 53% when compared with vehicle-treated controls, and AZD4547 at 12.5 mg/kg once daily or 6.25 mg/kg twice daily leads to complete tumor stasis, which is associated with dose proportional pharmacodynamic modulation of phospho-FGFR3 and reduced KMS11 tumor cell proliferation. Moreover, oral administration of AZD4547 at 12.5 mg/kg once daily results in 65% tumor growth inhibition in the FGFR1-fusion KG1a xenograft model. At efficacious dose levels, AZD4547 does not exhibit antiangiogenic effects. AZD4547 has no significant effect on blood pressure and therefore lacks in vivo anti-KDR activity. Consistently, dosing of 6.25 mg/kg orally twice daily AZD4547 is inactive in the cediranib-sensitive xenograft models including Calu-6, HCT-15 and LoVo. [1] |
Protocol
| Kinase Assay:[1] |
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AZD4547 kinase activity: The ability of AZD4547 to inhibit the human recombinant kinase activities of FGFR1-3 is tested using ATP concentrations at, or just below, the respective Km. |
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| Cell Research:[1] |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | DMSO | 92 mg/mL (198.45 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 4% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing. |
5mg/mL |
* 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 Information
| Molecular Weight | 463.57 |
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| Formula | C26H33N5O3 |
| CAS No. | 1035270-39-3 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
Bio Calculators
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Molecular Weight Calculator
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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
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Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Molarity Calculator
Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT02824133 | Suspended | Recurrent IDHwt Gliomas With FGFR3-TACC3 Fusion|Recurrent IDHwt Gliomas With FGFR1-TACC1 Fusion | Assistance Publique - Hôpitaux de Paris | September 2015 | Phase 1|Phase 2 |
| NCT01824901 | Completed | Recurrent Non-small Cell Lung Cancer|Squamous Cell Lung Cancer | ECOG-ACRIN Cancer Research Group|National Cancer Institute (NCI)|Eastern Cooperative Oncology Group | September 2013 | Phase 1|Phase 2 |
| NCT01795768 | Unknown status | Gastric Cancer|Oesophageal Cancer|Breast Cancer|Squamous Cell Carcinoma of the Lung | Royal Marsden NHS Foundation Trust|AstraZeneca | September 2012 | Phase 2 |
| NCT01791985 | Active not recruiting | Breast Cancer | Imperial College London|Cancer Research UK|AstraZeneca | July 2012 | Phase 1|Phase 2 |
| NCT01457846 | Terminated | Gastro-oesophageal Junction Cancer|Gastric Cancer | AstraZeneca | November 2011 | Phase 2 |
| NCT01202591 | Completed | FGFR Inhibition Pharmacokinetics Biomarkers|ER+ Breast Cancer | AstraZeneca | December 2010 | Phase 1|Phase 2 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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