1. Cell Cycle/DNA Damage
    Epigenetics
    Protein Tyrosine Kinase/RTK
  2. Aurora Kinase
    VEGFR

PF-03814735 

Cat. No.: HY-14574 Purity: 99.77%
Handling Instructions

PF-03814735 is a potent, orally available 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 (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 132 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 120 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 216 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 720 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
100 mg   Get quote  
200 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

PF-03814735 is a potent, orally available 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].

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].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume 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.
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]

PF03814735 is formulated as a solution in cremophor EL [cremophor/ethanol/0.9% saline (12.5%/12.5%/ 75%)][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
Molecular Weight

474.48

Formula

C₂₃H₂₅F₃N₆O₂

CAS No.

942487-16-3

SMILES

O=C(CNC(C)=O)N1[[email protected]@H]2C3=C(C=C(NC4=NC(NC5CCC5)=C(C(F)(F)F)C=N4)C=C3)[[email protected]]1CC2

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 47 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.77%

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Product Name:
PF-03814735
Cat. No.:
HY-14574
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