PF-03814735
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MedKoo CAT#: 205987

CAS#: 942487-16-3

Description: 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

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PF-03814735
CAS# 942487-16-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205987
Name: PF-03814735
CAS#: 942487-16-3
Chemical Formula: C23H25F3N6O2
Exact Mass: 474.20
Molecular Weight: 474.488
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 2 Weeks
10mg USD 480 2 Weeks
50mg USD 1160 2 Weeks
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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

More Info:         

Product Data:
Product Data
Instruction:
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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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

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.

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1: 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. PubMed PMID: 22222631.

2: 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. PubMed PMID: 21852114.

3: 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. PubMed PMID: 20354118.

4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Sep;30(7):543-88. PubMed PMID: 18985183.