F-14512 (free base)

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

MedKoo CAT#: 529709

CAS#: 866874-63-7 (free base)

Description: F-14512 is a DNA topoisomerase II inhibitor potentially for the treatment of acute myeloid leukemia.


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F-14512 is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 529709
Name: F-14512 (free base)
CAS#: 866874-63-7 (free base)
Chemical Formula: C33H47N5O8
Exact Mass: 641.3425
Molecular Weight: 641.76
Elemental Analysis: C, 61.76; H, 7.38; N, 10.91; O, 19.94


Related CAS #: 866874-39-7 (HCl)   866874-63-7 (free base)    

Synonym: F-14512; F14512; F14512

IUPAC/Chemical Name: 2-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-N-((5S,5aS,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)acetamide

InChi Key: NUZMJDHDPVKFJN-TYDXHICZSA-N

InChi Code: InChI=1S/C33H47N5O8/c1-42-26-13-20(14-27(43-2)32(26)40)29-21-15-24-25(46-19-45-24)16-22(21)31(23-18-44-33(41)30(23)29)38-28(39)17-37-12-6-11-36-9-4-3-8-35-10-5-7-34/h13-16,23,29-31,35-37,40H,3-12,17-19,34H2,1-2H3,(H,38,39)/t23-,29+,30-,31+/m0/s1

SMILES Code: O=C(N[C@H]1[C@]2([H])[C@@](C(OC2)=O)([H])[C@H](C3=CC(OC)=C(O)C(OC)=C3)C4=C1C=C5OCOC5=C4)CNCCCNCCCCNCCCN


Technical Data

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

Shelf Life:
>2 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).

Harmonized System Code:
293490


References

1: Tierny D, Serres F, Segaoula Z, Bemelmans I, Bouchaert E, Pétain A, Brel V, Couffin S, Marchal T, Nguyen L, Thuru X, Ferré P, Guilbaud N, Gomes B. Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma. Clin Cancer Res. 2015 Dec 1;21(23):5314-23. doi: 10.1158/1078-0432.CCR-14-3174. PubMed PMID: 26169968.

2: Mouawad F, Gros A, Rysman B, Bal-Mahieu C, Bertheau C, Horn S, Sarrazin T, Lartigau E, Chevalier D, Bailly C, Lansiaux A, Meignan S. The antitumor drug F14512 enhances cisplatin and ionizing radiation effects in head and neck squamous carcinoma cell lines. Oral Oncol. 2014 Feb;50(2):113-9. doi: 10.1016/j.oraloncology.2013.11.003. PubMed PMID: 24290982.

3: Leblond P, Boulet E, Bal-Mahieu C, Pillon A, Kruczynski A, Guilbaud N, Bailly C, Sarrazin T, Lartigau E, Lansiaux A, Meignan S. Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines. Invest New Drugs. 2014 Oct;32(5):883-92. doi: 10.1007/s10637-014-0132-3. PubMed PMID: 25008900.

4: Thibault B, Clement E, Zorza G, Meignan S, Delord JP, Couderc B, Bailly C, Narducci F, Vandenberghe I, Kruczynski A, Guilbaud N, Ferré P, Annereau JP. F14512, a polyamine-vectorized inhibitor of topoisomerase II, exhibits a marked anti-tumor activity in ovarian cancer. Cancer Lett. 2016 Jan 1;370(1):10-8. doi: 10.1016/j.canlet.2015.09.006. PubMed PMID: 26404751.

5: Kruczynski A, Pillon A, Créancier L, Vandenberghe I, Gomes B, Brel V, Fournier E, Annereau JP, Currie E, Guminski Y, Bonnet D, Bailly C, Guilbaud N. F14512, a polyamine-vectorized anti-cancer drug, currently in clinical trials exhibits a marked preclinical anti-leukemic activity. Leukemia. 2013 Nov;27(11):2139-48. doi: 10.1038/leu.2013.108. PubMed PMID: 23568148.

6: Ballot C, Jendoubi M, Kluza J, Jonneaux A, Laine W, Formstecher P, Bailly C, Marchetti P. Regulation by survivin of cancer cell death induced by F14512, a polyamine-containing inhibitor of DNA topoisomerase II. Apoptosis. 2012 Apr;17(4):364-76. doi: 10.1007/s10495-011-0681-2. PubMed PMID: 22127645.

7: Brel V, Annereau JP, Vispé S, Kruczynski A, Bailly C, Guilbaud N. Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II. Biochem Pharmacol. 2011 Dec 15;82(12):1843-52. doi: 10.1016/j.bcp.2011.08.028. PubMed PMID: 21924246.

8: Gentry AC, Pitts SL, Jablonsky MJ, Bailly C, Graves DE, Osheroff N. Interactions between the etoposide derivative F14512 and human type II topoisomerases: implications for the C4 spermine moiety in promoting enzyme-mediated DNA cleavage. Biochemistry. 2011 Apr 19;50(15):3240-9. doi: 10.1021/bi200094z. PubMed PMID: 21413765; PubMed Central PMCID: PMC3086367.

9: Kruczynski A, Vandenberghe I, Pillon A, Pesnel S, Goetsch L, Barret JM, Guminski Y, Le Pape A, Imbert T, Bailly C, Guilbaud N. Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system. Invest New Drugs. 2011 Feb;29(1):9-21. doi: 10.1007/s10637-009-9328-3. PubMed PMID: 19777159.

10: Chelouah S, Monod-Wissler C, Bailly C, Barret JM, Guilbaud N, Vispé S, Käs E. An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II. PLoS One. 2011;6(8):e23597. doi: 10.1371/journal.pone.0023597. PubMed PMID: 21853156; PubMed Central PMCID: PMC3154508.

11: Barret JM, Kruczynski A, Vispé S, Annereau JP, Brel V, Guminski Y, Delcros JG, Lansiaux A, Guilbaud N, Imbert T, Bailly C. F14512, a potent antitumor agent targeting topoisomerase II vectored into cancer cells via the polyamine transport system. Cancer Res. 2008 Dec 1;68(23):9845-53. doi: 10.1158/0008-5472.CAN-08-2748. PubMed PMID: 19047165.

12: Annereau JP, Brel V, Dumontet C, Guminski Y, Imbert T, Broussas M, Vispé S, Bréand S, Guilbaud N, Barret JM, Bailly C. A fluorescent biomarker of the polyamine transport system to select patients with AML for F14512 treatment. Leuk Res. 2010 Oct;34(10):1383-9. doi: 10.1016/j.leukres.2009.12.021. PubMed PMID: 20096930.

13: Palermo G, Minniti E, Greco ML, Riccardi L, Simoni E, Convertino M, Marchetti C, Rosini M, Sissi C, Minarini A, De Vivo M. An optimized polyamine moiety boosts the potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512. Chem Commun (Camb). 2015 Oct 1;51(76):14310-3. doi: 10.1039/c5cc05065k. PubMed PMID: 26234198.

14: Pesnel S, Guminski Y, Pillon A, Lerondel S, Imbert T, Guilbaud N, Kruczynski A, Bailly C, Le Pape A. 99mTc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation. Eur J Nucl Med Mol Imaging. 2011 Oct;38(10):1832-41. doi: 10.1007/s00259-011-1857-2. PubMed PMID: 21660624.