PF-03814735
Based on 2 publication(s) in Google Scholar
PF-03814735 is a potent, orally available, ATP-competitive and reversible aurora A and aurora B inhibitor with IC50s of 0.8 and 0.5 nM, respectively.
For research use only. We do not sell to patients.
- Purity: 99.45%
- CAS No.: 942487-16-3
- Formula: C23H25F3N6O2
- Molecular Weight:474.48
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PF-03814735
MoreAll Aurora Kinase Isoforms
MoreAll VEGFR Isoforms
More
Biological Activity
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Aurora 1 0.8 nM (IC50) |
Aurora 2 5 nM (IC50) |
Flt-1 10 nM (IC50) |
FAK 22 nM (IC50) |
TrkA 30 nM (IC50) |
Met 100 nM (IC50) |
FGFR1 100 nM (IC50) |
In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells[1]. Small cell lung cancer (SCLC) and, to a lesser extent, colon cancer lines are very sensitive to PF-03814735. The status of the Myc gene family and retinoblastoma pathway members significantly correlates with the efficacy of PF-03814735[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 942487-16-3
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Appearance Solid
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Molecular Weight 474.48
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Formula C23H25F3N6O2
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Color White to off-white
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SMILES
O=C(CNC(C)=O)N1[C@@H]2C3=C(C=C(NC4=NC(NC5CCC5)=C(C(F)(F)F)C=N4)C=C3)[C@H]1CC2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (2)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Solvent & Solubility
DMSO : ≥ 100 mg/mL (210.76 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.27 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.27 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Aurora1 and Aurora2 proteins are produced as full-length His-tag recombinant proteins expressed in insect cells. For the Aurora2 kinase assay, phosphorylation of the substrate peptide by recombinant Aurora2 protein is assessed at 3 to 300 μM ATP and various concentrations of PF-03814735 over 60 min, at a substrate peptide concentration of 2 μM. Phosphorylation is linear over this time for all conditions. For the Aurora1 kinase assay, phosphorylation of the substrate peptide by recombinant Aurora1 protein is assessed by a scintillation proximity assay in a 96-well plate format in which the incorporation of 33P into the peptide substrate is measured by capturing the peptide on a streptavidin scintillation proximity assay bead[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell lines are grown in appropriate media and evaluated after 48 h of exposure to either PF-03814735 or vehicle. Proliferation (as measured by an increase in cell number) is expressed as a percent of untreated controls. To evaluate the PF-03814735 exposure time required for antiproliferative activity, HL-60 cell cultures are cultured in RPMI medium supplemented with 15% heat-inactivated fetal bovine serum and exposed to various PF-03814735 concentrations for 4, 8, 12, 24, and 48 h, followed by a washout step and incubation with growth media without PF-03814735 for the remainder of the 72-h assay period. Continuous exposure to PF-03814735 for 72 h is also evaluated. Cell counts are determined by a Coulter Counter[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice: Mice bearing s.c. HCT-116 xenograft tumors (250-400mm3) are evaluated for plasma drug concentrations and tumor levels of phosphohistone H3 Ser10. Mice are treated with a single dose of PF-03814735 or vehicle by oral gavage and are sacrificed at 0.5, 1, 2, 3, 7, 16, or 24 h postdose (3-4 mice/time point)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Jani JP, et al. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94. [Content Brief]
[2]. Hook KE, et al. An integrated genomic approach to identify predictive biomarkers of response to the aurora kinase inhibitor PF-03814735. Mol Cancer Ther. 2012 Mar;11(3):710-9. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1076 mL | 10.5379 mL | 21.0757 mL | 52.6893 mL |
| 5 mM | 0.4215 mL | 2.1076 mL | 4.2151 mL | 10.5379 mL | |
| 10 mM | 0.2108 mL | 1.0538 mL | 2.1076 mL | 5.2689 mL | |
| 15 mM | 0.1405 mL | 0.7025 mL | 1.4050 mL | 3.5126 mL | |
| 20 mM | 0.1054 mL | 0.5269 mL | 1.0538 mL | 2.6345 mL | |
| 25 mM | 0.0843 mL | 0.4215 mL | 0.8430 mL | 2.1076 mL | |
| 30 mM | 0.0703 mL | 0.3513 mL | 0.7025 mL | 1.7563 mL | |
| 40 mM | 0.0527 mL | 0.2634 mL | 0.5269 mL | 1.3172 mL | |
| 50 mM | 0.0422 mL | 0.2108 mL | 0.4215 mL | 1.0538 mL | |
| 60 mM | 0.0351 mL | 0.1756 mL | 0.3513 mL | 0.8782 mL | |
| 80 mM | 0.0263 mL | 0.1317 mL | 0.2634 mL | 0.6586 mL | |
| 100 mM | 0.0211 mL | 0.1054 mL | 0.2108 mL | 0.5269 mL |
PF-03814735 Related Classifications
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