1. Cell Cycle/DNA Damage Epigenetics Protein Tyrosine Kinase/RTK
  2. Aurora Kinase VEGFR
  3. PF-03814735

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.

PF-03814735 Chemical Structure

PF-03814735 Chemical Structure

CAS No. : 942487-16-3

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 110 In-stock
Solution
10 mM * 1 mL in DMSO USD 110 In-stock
Solid
5 mg USD 105 In-stock
10 mg USD 168 In-stock
50 mg USD 720 In-stock
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Based on 2 publication(s) in Google Scholar

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  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

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.

IC50 & Target[1]

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 Vitro

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.

In Vivo

Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition[1]. PF-03814735 is much more effective in NCI-H82 xenografts when administered on a weekly dosing schedule at 80 mg/kg compared with a daily schedule at 15 mg/kg. PF-03814735 delayed growth by 23.5 days on the weekly schedule, which corresponds to 0.9 logs of net cell kill during the course of treatment[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial
Molecular Weight

474.48

Formula

C23H25F3N6O2

CAS No.
Appearance

Solid

Color

White to off-white

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

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.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.1076 mL 10.5379 mL 21.0757 mL
5 mM 0.4215 mL 2.1076 mL 4.2151 mL
View the 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.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation

Purity: 99.58%

References
Kinase Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

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
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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PF-03814735
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