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

PF-03814735 

Cat. No.: HY-14574 Purity: 99.58%
COA Handling Instructions

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

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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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Customer Review

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)

*"≥" 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
10 mM 0.2108 mL 1.0538 mL 2.1076 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 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

  • 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

  • 3.

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.27 mM); Clear solution

*All of the co-solvents are available by MedChemExpress (MCE).
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
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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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Product Name:
PF-03814735
Cat. No.:
HY-14574
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