Troxacitabine

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

MedKoo CAT#: 203030

CAS#: 145918-75-8

Description: Troxacitabine, also known as BCH-4556; SGX-145; SPD-758; beta-L-OddC, is a DNA polymerase inhibitor potentially for the treatment of acute myeloid leukemia (AML) and solid. In comparison with gemcitabine, troxacitabine was more efficacious against Panc-01 and was equally active against MiaPaCa. Troxacitabine has a unique metabolic and pharmacokinetic profile and significant antileukemic activity. Troxacitabine merits further study in hematologic malignancies.


Chemical Structure

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Troxacitabine
CAS# 145918-75-8

Theoretical Analysis

MedKoo Cat#: 203030
Name: Troxacitabine
CAS#: 145918-75-8
Chemical Formula: C8H11N3O4
Exact Mass: 213.07496
Molecular Weight: 213.19
Elemental Analysis: C, 45.07; H, 5.20; N, 19.71; O, 30.02

Size Price Shipping out time Quantity
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Pricing updated 2021-03-05. Prices are subject to change without notice.

Troxacitabine 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.

Synonym: Troxacitabine; BCH-4556; SGX-145; SPD-758; beta-L-OddC; BCH4556; SGX145; SPD758; brand name Troxatyl.

IUPAC/Chemical Name: 4-amino-1-[(2S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]pyrimidin-2-one.

InChi Key: RXRGZNYSEHTMHC-MLWJPKLSSA-N

InChi Code: InChI=1S/C8H11N3O4/c9-5-1-2-11(8(13)10-5)6-4-14-7(3-12)15-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6?,7-/m0/s1

SMILES Code: O=C1N=C(N)C=CN1C2O[C@@H](CO)OC2

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 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

Safety Data Sheet (SDS):

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 213.19 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.

Select a batch to recalculate based on the batch molecular weight:
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

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1: Adema AD, Floor K, Smid K, Honeywell RJ, Scheffer GL, Jansen G, Peters GJ. Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine. Springerplus. 2014 Dec 13;3:732. doi: 10.1186/2193-1801-3-732. eCollection 2014. PubMed PMID: 25674464; PubMed Central PMCID: PMC4320143.

2: Ng CM, Patnaik A, Beeram M, Lin CC, Takimoto CH. Mechanism-based pharmacokinetic/pharmacodynamic model for troxacitabine-induced neutropenia in cancer patients. Cancer Chemother Pharmacol. 2011 May;67(5):985-94. doi: 10.1007/s00280-010-1393-y. Epub 2010 Jul 8. PubMed PMID: 20614121.

3: Lin CC, Beeram M, Rowinsky EK, Takimoto CH, Ng CM, Geyer CE Jr, Denis LJ, De Bono JS, Hao D, Tolcher AW, Rha SY, Jolivet J, Patnaik A. Phase I and pharmacokinetic study of cisplatin and troxacitabine administered intravenously every 28 days in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2009 Dec;65(1):167-75. doi: 10.1007/s00280-009-1020-y. Epub 2009 May 16. PubMed PMID: 19449006.

4: Lam W, Bussom S, Cheng YC. Effect of hypoxia on the expression of phosphoglycerate kinase and antitumor activity of troxacitabine and gemcitabine in non-small cell lung carcinoma. Mol Cancer Ther. 2009 Feb;8(2):415-23. doi: 10.1158/1535-7163.MCT-08-0692. Epub 2009 Feb 10. PubMed PMID: 19208827.

5: Jimeno A, Messersmith WA, Lee CK, Ma WW, Laheru D, Donehower RC, Baker SD, Hidalgo M. Phase I study of troxacitabine administered by continuous infusion in subjects with advanced solid malignancies. Ann Oncol. 2008 Feb;19(2):374-9. doi: 10.1093/annonc/mdm572. PubMed PMID: 18245131; PubMed Central PMCID: PMC3557502.

6: Adema AD, Radi M, Daft J, Narayanasamy J, Hoebe EK, Alexander LE, Chu CK, Peters GJ. Troxacitabine prodrugs for pancreatic cancer. Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1073-7. PubMed PMID: 18058539.

7: Damaraju VL, Bouffard DY, Wong CK, Clarke ML, Mackey JR, Leblond L, Cass CE, Grey M, Gourdeau H. Synergistic activity of troxacitabine (Troxatyl) and gemcitabine in pancreatic cancer. BMC Cancer. 2007 Jul 3;7:121. PubMed PMID: 17608948; PubMed Central PMCID: PMC1948004.

8: Swords R, Apostolidou E, Giles F. Troxacitabine in leukemia. Hematology. 2006 Oct;11(5):321-9. Review. PubMed PMID: 17607581.

9: Lam W, Leung CH, Bussom S, Cheng YC. The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine. Mol Pharmacol. 2007 Sep;72(3):536-44. Epub 2007 Jun 12. PubMed PMID: 17565005.

10: Swords R, Giles F. Troxacitabine in acute leukemia. Hematology. 2007 Jun;12(3):219-27. Review. PubMed PMID: 17558697.

11: Radi M, Adema AD, Daft JR, Cho JH, Hoebe EK, Alexander LE, Peters GJ, Chu CK. In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs. J Med Chem. 2007 May 3;50(9):2249-53. Epub 2007 Apr 10. PubMed PMID: 17419604.

12: Quintás-Cardama A, Cortes J. Evaluation of the L-stereoisomeric nucleoside analog troxacitabine for the treatment of acute myeloid leukemia. Expert Opin Investig Drugs. 2007 Apr;16(4):547-57. Review. PubMed PMID: 17371201.

13: Vose JM, Panwalkar A, Belanger R, Coiffier B, Baccarani M, Gregory SA, Facon T, Fanin R, Caballero D, Ben-Yehuda D, Giles F. A phase II multicenter study of troxacitabine in relapsed or refractory lymphoproliferative neoplasms or multiple myeloma. Leuk Lymphoma. 2007 Jan;48(1):39-45. PubMed PMID: 17325846.

14: Sabini E, Hazra S, Konrad M, Burley SK, Lavie A. Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase. Nucleic Acids Res. 2007;35(1):186-92. Epub 2006 Dec 7. PubMed PMID: 17158155; PubMed Central PMCID: PMC1802566.

15: Roboz GJ, Giles FJ, Ritchie EK, Allen-Bard S, Curcio TJ, Wilkes MA, Park SL, Kantarjian HM, Faderl S, Ravandi F, Kelner MJ, Feldman EJ. Phase I/II study of continuous-infusion troxacitabine in refractory acute myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):10-5. Epub 2006 Dec 4. PubMed PMID: 17146106.

16: Adema AD, Zuurbier L, Floor K, Hubeek I, Kaspers GJ, Albertoni F, Peters GJ. Cellular resistance against troxacitabine in human cell lines and pediatric patient acute myeloid leukemia blast cells. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):981-6. PubMed PMID: 17065050.

17: Lee CK, Rowinsky EK, Li J, Giles F, Moore MJ, Hidalgo M, Capparelli E, Jolivet J, Baker SD. Population pharmacokinetics of troxacitabine, a novel dioxolane nucleoside analogue. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2158-65. PubMed PMID: 16609029.

18: Lam W, Park SY, Leung CH, Cheng YC. Apurinic/apyrimidinic endonuclease-1 protein level is associated with the cytotoxicity of L-configuration deoxycytidine analogs (troxacitabine and beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine) but not D-configuration deoxycytidine analogs (gemcitabine and beta-D-arabinofuranosylcytosine). Mol Pharmacol. 2006 May;69(5):1607-14. Epub 2006 Feb 15. PubMed PMID: 16481390.

19: Dent SF, Arnold A, Stewart DJ, Gertler S, Ayoub J, Batist G, Goss G, Nevile A, Soulieres D, Jolivet J, McLntosh L, Seymour L. Phase II study of troxacitabine (BCH-4556) in patients with advanced non-small-cell lung cancer. Lung. 2005 Jul-Aug;183(4):265-72. PubMed PMID: 16211462.

20: Lapointe R, Létourneau R, Steward W, Hawkins RE, Batist G, Vincent M, Whittom R, Eatock M, Jolivet J, Moore M. Phase II study of troxacitabine in chemotherapy-naive patients with advanced cancer of the pancreas: gastrointestinal tumors. Ann Oncol. 2005 Feb;16(2):289-93. PubMed PMID: 15668286.



Additional Information

Troxacitabine is a dioxolane derivative and a novel L-configuration deoxycytidine analogue with potent antineoplastic activity. When incorporated into growing chain during DNA replication, troxacitabine stops DNA polymerization due to its unnatural L-configuration, in contrast to the normal nucleotides with D-configuration. As a result, this agent terminates DNA synthesis upon incorporated into DNA molecules, and consequently interrupts tumor cell proliferation. (from NCI's webpage)
 
Current developer:      SGX Pharmaceuticals, Inc.