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PF-03814735Aurora A/B inhibitor

PF-03814735

Catalog No. A4128
Size Price Stock Qty
5mg $165.00 In stock
10mg $275.00 In stock
50mg $670.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

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Chemical structure

PF-03814735

Biological Activity

Description PF-03814735 is a novel, potent and reversible inhibitor of Aurora A and B with IC50 values of 20 nM and 150 nM, respectively.
Targets Aurora A Aurora B        
IC50 20 nM 150 nM        

Protocol

Cell experiment [1]:

Cell lines

MDA-MB-231 cells, various tumor types (HCT-116, HL-60, A549, and H125) as well as tumor cell lines of rat (C6), mouse (L1210), and dog (MDCK) origin.

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.

Reacting condition

1-1000 nM; 4, 8, 12, 24, and 48 h

Applications

In MDA-MB-231 cells, PF-03814735 markedly reduced levels of Aurora1 phosphorylated on Thr 232 and the phosphorylation of histone H3 on Ser10 with IC50 values of 20 nmol/L and 50 nmol/L. In various tumor cell lines, PF-03814735 resulted in a reduction in cell number with IC50 values ranging from 42 to 150 nmol/L. PF-03814735 at 300 nmol/L produced near-complete inhibition of cell proliferation.

Animal experiment [1]:

Animal models

Athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts

Dosage form

10, 20, and 30 mg/kg; oral gavage for 10 days

Application

In athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts, PF-03814735 (≥20 mg/kg) resulted in statistically significant and dose-dependent tumor growth inhibition of ≥50% relative to vehicle-treated mice. The tumor growth inhibition was associated with a reduction in phosphorylated histone H3 levels of ≥50% for approximately 5 hours each day for 10 days.

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.

References:

[1] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.

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Chemical Properties

Cas No. 942487-16-3 SDF Download SDF
Canonical SMILES CC(=O)NCC(=O)N1C2CCC1C3=C2C=CC(=C3)NC4=NC=C(C(=N4)NC5CCC5)C(F)(F)F
Formula C23H25F3N6O2 M.Wt 474.48
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips N/A
Shipping Condition N/A

Background

PF-03814735 is a potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases with IC50 values of 0.8nM and 5nM, respectively [1].

PF-03814735 is an ATP competitive inhibitor of Aurora kinases. It also shows inhibition of other protein kinases at 100nM, such as Flt1, FAK, TrkA, Met, and FGFR1. The immunofluorescence imaging analysis shows PF-03814735 can inhibit the phosphorylation of Aurora1, Aurora 2 as well as histone H3 in MDA-MB-231 cells. This inhibition is rapid and reversible. The inhibition of phosphorylated histone H3 also occurs in athymic mice bearing HCT-116 xenografts. PF-03814735 induces the formation of polyploid cells and multinucleated cells due to the block in cytokinesis secondary. Moreover, PF-03814735 treatment results in a reduction of cell proliferation in vitro (such as HL-60, A549, and H125) and a inhibition of tumor growth in vivo (human xenograft mouse models, such as A2780 ovarian carcinoma and HCT-116) [1].

References:
[1] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.