AZD4547
AZD4547 (CAS: 1035270-39-3) is an orally bioavailable inhibitor targeting fibroblast growth factor receptors (FGFRs). It selectively inhibits FGFR1, FGFR2, and FGFR3 tyrosine kinase activities, exhibiting IC50 values of 12 nM, 2 nM, and 40 nM, respectively, and potently reduces their autophosphorylation. AZD4547 treatment in breast cancer (Sum52-PE), multiple myeloma (KMS11), and acute myeloid leukemia (KG1a) cells decreases proliferation and FGFR downstream signal phosphorylation. Preclinical studies in lung cancer xenograft models illustrate its antitumor efficacy associated with selective FGFR inhibition, highlighting its research utility in studying FGFR-related oncology.
- 1. Hugh A. Nicholson, Lynne Sawers, et al. "Fibroblast growth factor signalling influences homologous recombination-mediated DNA damage repair to promote drug resistance in ovarian cancer." Br J Cancer. 2022 Oct;127(7):1340-1351. PMID: 35778553
- 2. Day EK, Sosale NG, et al. "Glioblastoma Cell Resistance to EGFR and MET Inhibition Can Be Overcome via Blockade of FGFR-SPRY2 Bypass Signaling." Cell Rep. 2020;30(10):3383-3396.e7. PMID: 32160544
- 3. Else Driehuis. "Organoids as a tool for fundamental and translational oncology research: Can organoids guide clinical decision making?" Universiteit Utrecht. 2019.
- 4. Driehuis E, Kolders S, et al. "Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy." Cancer Discov. 2019 Jul;9(7):852-871. PMID: 31053628
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 463.57 |
| Cas No. | 1035270-39-3 |
| Formula | C26H33N5O3 |
| Synonyms | AZD 4547;AZD-4547 |
| Solubility | ≥23.2 mg/mL in DMSO; insoluble in H2O; ≥6.33 mg/mL in EtOH |
| Chemical Name | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC1CN(CC(N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC |
| 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. |
| Kinase experiment [1]: | |
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AZD4547 kinase activity |
The ability of AZD4547 to inhibit the human recombinant kinase activities of FGFR1-3 was tested using ATP concentrations at, or just below, the respective Km. |
| Cell experiment [1]: | |
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Cell lines |
KG1a, Sum52-PE, KMS11 and MCF7 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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 μM; 72 hrs |
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Applications |
AZD4547 affected AKT phosphorylation in Sum52-PE and MCF7 cells, but not in KG1a and KMS11 cells. AZD4547 treatment significantly induced apoptosis in Sum52-PE and KMS11 cells, and dramatically increased G1 arrest but not apoptosis in KG1a cells. In MCF7 cells, AZD4547 showed no effect on cell cycle distribution or apoptosis. |
| Animal experiment [1]: | |
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Animal models |
SCID mice bearing KMS11 tumors |
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Dosage form |
1.5 ~ 12.5 mg/kg, p.o.; q.d. or b.i.d. |
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Applications |
In mice bearing KMS11 tumors, AZD4547 (3 mg/kg, b.i.d.) significantly inhibited tumor growth (53%). AZD4547 treatment at 12.5 mg/kg once daily or 6.25 mg/kg twice daily resulted in complete tumor stasis due to dose-dependent modulation of phospho-FGFR3, and reduced KMS11 cell proliferation. |
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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]. Gavine PR, Mooney L, Kilgour E, Thomas AP, Al-Kadhimi K, Beck S, Rooney C, Coleman T, Baker D, Mellor MJ, Brooks AN, Klinowska T. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res.2012 Apr 15;72(8):2045-56. |
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| Description | AZD4547 is a novel selective inhibitor of FGFR for FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM, weaker activity against FGFR4, VEGFR2(KDR), and little activity observed against IGFR, CDK2, and p38. | |||||
| Targets | FGFR1 | FGFR2 | FGFR3 | |||
| IC50 | 0.2 nM | 2.5 nM | 1.8 nM | |||
Quality Control & MSDS
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