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| 25mg |
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Purity: ≥98%
PF-03814735 (PF03814735) is a reversible, orally bioavailable, and ATP-competitive inhibitor of Aurora A/B kinases with potential antitumor activity. It inhibits Aurora A/B with IC50of 0.8 nM and 5 nM, respectively. PF-03814735 showed less potency against Flt3, FAK, TrkA, Met and FGFR1. It exhibits potent in vitro antiproliferative activity and high in vivo antitumor efficacy.
| ln Vitro |
Phosphorylated Aurora1, phosphorylated histone H3, and phosphorylated Aurora2 were all less abundant in intact cells as a result of PF-03814735's inhibitory action on the Aurora1 and Aurora2 kinases. The development of polyploid multinucleated cells and cell proliferation are inhibited by PF-03814735 because it suppresses cytokinesis [1]. High sensitivity to PF-03814735 has been shown in cell lines of small cell lung cancer (SCLC) and, to a lesser extent, colon cancer. There exists a substantial correlation between the effectiveness of PF-03814735 and the status of members of the retinoblastoma pathway and the Myc gene family.
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| ln Vivo |
When PF-03814735 was given orally once a day to mice with human xenograft tumors, it dramatically slowed down the growth of the tumors by lowering the levels of phosphorylated histone H3 to levels that were manageable. In xenograft mice tumor models, the combination of docetaxel and PF-03814735 showed synergistic tumor growth suppression [1]. When given as a weekly regimen of 80 mg/kg instead of a daily regimen of 15 mg/kg, PF-03814735 was more successful in NCI-H82 xenografts. Weekly growth delays of 23.5 days caused by PF-03814735 equate to 0.9 log net cell death throughout treatment [2].
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| 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.
[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 |
| Molecular Formula |
C23H25F3N6O2
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| Molecular Weight |
474.48
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| CAS # |
942487-16-3
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| Related CAS # |
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| SMILES |
CC(NCC(N1[C@@]2([H])CC[C@]1([H])C3=C2C=CC(NC4=NC=C(C(F)(F)F)C(NC5CCC5)=N4)=C3)=O)=O
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| InChi Key |
RYYNGWLOYLRZLK-RBUKOAKNSA-N
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| InChi Code |
InChI=1S/C23H25F3N6O2/c1-12(33)27-11-20(34)32-18-7-8-19(32)16-9-14(5-6-15(16)18)30-22-28-10-17(23(24,25)26)21(31-22)29-13-3-2-4-13/h5-6,9-10,13,18-19H,2-4,7-8,11H2,1H3,(H,27,33)(H2,28,29,30,31)/t18-,19+/m0/s1
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| Chemical Name |
N-(2-((1S,4R)-6-((4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,2,3,4-tetrahydro-1,4-epiminonaphthalen-9-yl)-2-oxoethyl)acetamide
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| Synonyms |
PF-03814735; PF 03814735; PF03814735
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% Cremophor EL, 2% N,N-dimethylacetamide, pH 5.0: ~30mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00424632 | Completed Has Results | Drug: PF-03814735 | Solid Tumors | Pfizer | November 2006 | Phase 1 |
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