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MedKoo Cat#: 205987 | Name: PF-03814735
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-03814735 is an orally bioavailable, ATP-competitive, reversible small-molecule Aurora kinase inhibitor with potential antineoplastic activity. Aurora kinase inhibitor PF-03814735 binds to and inhibits Aurora kinases A and B, which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis.

Chemical Structure

PF-03814735
PF-03814735
CAS#942487-16-3

Theoretical Analysis

MedKoo Cat#: 205987

Name: PF-03814735

CAS#: 942487-16-3

Chemical Formula: C23H25F3N6O2

Exact Mass: 474.1991

Molecular Weight: 474.49

Elemental Analysis: C, 58.22; H, 5.31; F, 12.01; N, 17.71; O, 6.74

Price and Availability

Size Price Availability Quantity
5mg USD 260.00 2 Weeks
10mg USD 480.00 2 Weeks
50mg USD 1,160.00 2 Weeks
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Related CAS #
No Data
Synonym
PF03814735; PF-03814735; PF 03814735.
IUPAC/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
InChi Key
RYYNGWLOYLRZLK-RBUKOAKNSA-N
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
SMILES Code
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
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
soluble in DMSO, not soluble in water.
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
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Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-03814735 is a potent, orally available, ATP-competitive and reversible aurora A and aurora B inhibitor with IC50 s of 0.8 and 0.5 nM.
In vitro activity:
PF-03814735, a small-molecule inhibitor of Aurora kinase A (IC50 = 0.8 nM) and B (IC50 = 5 nM), was the most potent on KTC2 cells, whereas CUDC-101, a multitarget inhibitor, was effective on both WRO and KTC2 cells. Notably, PF-03814735 was found to be the most effective epigenetic drug on cell lines harboring the C228T mutation. In conclusion, these new findings offer specific guidance on dose and time course selection to design novel therapeutic interventions against TC using PF-03814735, and specifically target cells carrying the TERTpC228T mutation. Reference: OMICS. 2019 Oct;23(10):486-495. https://pubmed.ncbi.nlm.nih.gov/31549911/
In vivo activity:
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. These results support the clinical evaluation of PF-03814735 in cancer patients. Reference: Mol Cancer Ther. 2010 Apr;9(4):883-94. https://pubmed.ncbi.nlm.nih.gov/20354118/
Solvent mg/mL mM
Solubility
DMF 20.0 42.15
DMSO 54.5 114.38
Ethanol 14.8 31.08
Ethanol:PBS (pH 7.2) (1:9) 0.1 0.21
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 474.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Dalva-Aydemir S, Akyerli CB, Yüksel ŞK, Keskin H, Yakıcıer MC. Toward In Vitro Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor. OMICS. 2019 Oct;23(10):486-495. doi: 10.1089/omi.2019.0050. Epub 2019 Sep 24. PMID: 31549911. 2. 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. doi: 10.1158/1535-7163.MCT-09-0915. Epub 2010 Mar 30. PMID: 20354118.
In vitro protocol:
1. Dalva-Aydemir S, Akyerli CB, Yüksel ŞK, Keskin H, Yakıcıer MC. Toward In Vitro Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor. OMICS. 2019 Oct;23(10):486-495. doi: 10.1089/omi.2019.0050. Epub 2019 Sep 24. PMID: 31549911.
In vivo protocol:
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. doi: 10.1158/1535-7163.MCT-09-0915. Epub 2010 Mar 30. PMID: 20354118.
1: Thawornkuno C, Srisuksai K, Simanon N, Adisakwattana P, Ampawong S, Boonyuen U, Limpanont Y, Chusongsang P, Chusongsang Y, Kiangkoo N, Reamtong O. A reanalysis and integration of transcriptomics and proteomics datasets unveil novel drug targets for Mekong schistosomiasis. Sci Rep. 2024 Jun 5;14(1):12969. doi: 10.1038/s41598-024-63869-0. PMID: 38839835; PMCID: PMC11153569. 2: Ly CY, Pfannenstiel J, Pant A, Yang Z, Fehr AR, Rodzkin MS, Davido DJ. Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles. Microbiol Spectr. 2023 Feb 14;11(1):e0194322. doi: 10.1128/spectrum.01943-22. Epub 2022 Dec 20. PMID: 36537798; PMCID: PMC9927324. 3: Small JC, Joblin-Mills A, Carbone K, Kost-Alimova M, Ayukawa K, Khodier C, Dancik V, Clemons PA, Munkacsi AB, Wagner BK. Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity. ACS Chem Biol. 2022 May 20;17(5):1131-1142. doi: 10.1021/acschembio.2c00052. Epub 2022 Apr 19. PMID: 35439415; PMCID: PMC9127801. 4: Trieger KA, La Clair JJ, Burkart MD. Splice Modulation Synergizes Cell Cycle Inhibition. ACS Chem Biol. 2020 Mar 20;15(3):669-674. doi: 10.1021/acschembio.9b00833. Epub 2020 Feb 17. PMID: 32004428; PMCID: PMC7570451. 5: Dalva-Aydemir S, Akyerli CB, Yüksel ŞK, Keskin H, Yakıcıer MC. Toward In Vitro Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor. OMICS. 2019 Oct;23(10):486-495. doi: 10.1089/omi.2019.0050. Epub 2019 Sep 24. PMID: 31549911. 6: Chi Q, Wang L, Xie D, Wang X. Characterization of in vitro metabolism of focal adhesion kinase inhibitors by LC/MS/MS. J Pharm Biomed Anal. 2019 May 10;168:163-173. doi: 10.1016/j.jpba.2019.02.028. Epub 2019 Feb 19. PMID: 30807921. 7: Falchook GS, Bastida CC, Kurzrock R. Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. Semin Oncol. 2015 Dec;42(6):832-48. doi: 10.1053/j.seminoncol.2015.09.022. Epub 2015 Sep 24. PMID: 26615129. 8: Sarvagalla S, Coumar MS. Structural Biology Insight for the Design of Sub- type Selective Aurora Kinase Inhibitors. Curr Cancer Drug Targets. 2015;15(5):375-93. doi: 10.2174/1568009615666150421110401. PMID: 25895501. 9: Hook KE, Garza SJ, Lira ME, Ching KA, Lee NV, Cao J, Yuan J, Ye J, Ozeck M, Shi ST, Zheng X, Rejto PA, Kan JL, Christensen JG, Pavlicek A. 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. doi: 10.1158/1535-7163.MCT-11-0184. Epub 2012 Jan 5. PMID: 22222631. 10: Schöffski P, Jones SF, Dumez H, Infante JR, Van Mieghem E, Fowst C, Gerletti P, Xu H, Jakubczak JL, English PA, Pierce KJ, Burris HA. Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. Eur J Cancer. 2011 Oct;47(15):2256-64. doi: 10.1016/j.ejca.2011.07.008. Epub 2011 Aug 16. PMID: 21852114. 11: 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. doi: 10.1158/1535-7163.MCT-09-0915. Epub 2010 Mar 30. PMID: 20354118. 12: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Sep;30(7):543-88. PMID: 18985183.