Sapacitabine
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MedKoo CAT#: 202560

CAS#: 151823-14-2

Description: Sapacitabine is an orally bioavailable pyrimidine analogue prodrug with potential antineoplastic activity. Sapacitabine is hydrolyzed by amidases to the deoxycytosine analogue CNDAC (2'-Cyano-2'-deoxyarabinofuranosylcytosine), which is then phosphorylated into the active triphosphate form. As an analogue of deoxycytidine triphosphate, CNDAC triphosphate incorporates into DNA strands during replication, resulting in single-stranded DNA breaks during polymerization due to beta-elimination during the fidelity checkpoint process; cell cycle arrest in the G2 phase and apoptosis ensue. The unmetabolized prodrug may exhibit antineoplastic activity as well.


Chemical Structure

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Sapacitabine
CAS# 151823-14-2

Theoretical Analysis

MedKoo Cat#: 202560
Name: Sapacitabine
CAS#: 151823-14-2
Chemical Formula: C26H42N4O5
Exact Mass: 490.31552
Molecular Weight: 490.63548
Elemental Analysis: C, 63.65; H, 8.63; N, 11.42; O, 16.30

Price and Availability

Size Price Availability Quantity
200.0mg USD 1850.0 2 Weeks
500.0mg USD 2850.0 2 Weeks
1.0g USD 3950.0 2 Weeks
2.0g USD 5450.0 2 Weeks
5.0g USD 9650.0 2 Weeks
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Synonym: CS682; CYC682; CYC-682; Sapacitabine

IUPAC/Chemical Name: N-(1-((2R,3S,4S,5R)-3-cyano-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)palmitamide

InChi Key: LBGFKUUHOPIEMA-PEARBKPGSA-N

InChi Code: InChI=1S/C26H42N4O5/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-23(32)28-22-16-17-30(26(34)29-22)25-20(18-27)24(33)21(19-31)35-25/h16-17,20-21,24-25,31,33H,2-15,19H2,1H3,(H,28,29,32,34)/t20-,21+,24-,25+/m0/s1

SMILES Code: CCCCCCCCCCCCCCCC(NC(C=CN1[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2C#N)=NC1=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

Preparing Stock Solutions

The following data is based on the product molecular weight 490.63548 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

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1: Kantarjian H, Faderl S, Garcia-Manero G, Luger S, Venugopal P, Maness L, Wetzler M, Coutre S, Stock W, Claxton D, Goldberg SL, Arellano M, Strickland SA, Seiter K, Schiller G, Jabbour E, Chiao J, Plunkett W. Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. Lancet Oncol. 2012 Nov;13(11):1096-104. doi: 10.1016/S1470-2045(12)70436-9. Epub 2012 Oct 15. PubMed PMID: 23075701.

2: Jagan S, Paganessi LA, Frank RR, Venugopal P, Larson M, Christopherson KW 2nd. Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine. Adv Hematol. 2012;2012:727683. doi: 10.1155/2012/727683. Epub 2012 Sep 23. PubMed PMID: 23049558; PubMed Central PMCID: PMC3461608.

3: Liu XJ, Nowak B, Wang YQ, Plunkett W. Sapacitabine, the prodrug of CNDAC, is a nucleoside analog with a unique action mechanism of inducing DNA strand breaks. Chin J Cancer. 2012 Aug;31(8):373-80. doi: 10.5732/cjc.012.10077. Epub 2012 Jun 26. PubMed PMID: 22739266.

4: Muggia F, Diaz I, Peters GJ. Nucleoside and nucleobase analogs in cancer treatment: not only sapacitabine, but also gemcitabine. Expert Opin Investig Drugs. 2012 Apr;21(4):403-8. doi: 10.1517/13543784.2012.666236. Epub 2012 Mar 9. PubMed PMID: 22404148.

5: Liu X, Kantarjian H, Plunkett W. Sapacitabine for cancer. Expert Opin Investig Drugs. 2012 Apr;21(4):541-55. doi: 10.1517/13543784.2012.660249. Epub 2012 Feb 14. Review. PubMed PMID: 22329458; PubMed Central PMCID: PMC3366487.

6: Green SR, Choudhary AK, Fleming IN. Combination of sapacitabine and HDAC inhibitors stimulates cell death in AML and other tumour types. Br J Cancer. 2010 Oct 26;103(9):1391-9. doi: 10.1038/sj.bjc.6605922. Epub 2010 Oct 5. PubMed PMID: 20924380; PubMed Central PMCID: PMC2990608.

7: Kantarjian H, Garcia-Manero G, O'Brien S, Faderl S, Ravandi F, Westwood R, Green SR, Chiao JH, Boone PA, Cortes J, Plunkett W. Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome. J Clin Oncol. 2010 Jan 10;28(2):285-91. doi: 10.1200/JCO.2009.25.0209. Epub 2009 Nov 23. PubMed PMID: 19933907; PubMed Central PMCID: PMC3340938.

8: Serova M, Galmarini CM, Ghoul A, Benhadji K, Green SR, Chiao J, Faivre S, Cvitkovic E, Le Tourneau C, Calvo F, Raymond E. Antiproliferative effects of sapacitabine (CYC682), a novel 2'-deoxycytidine-derivative, in human cancer cells. Br J Cancer. 2007 Sep 3;97(5):628-36. Epub 2007 Jul 17. PubMed PMID: 17637678; PubMed Central PMCID: PMC2360357.

9: Galmarini CM. Drug evaluation: sapacitabine--an orally available antimetabolite in the treatment of cancer. Curr Opin Investig Drugs. 2006 Jun;7(6):565-73. PubMed PMID: 16784028.



Additional Information

 
Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in both blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (Gemzar®; Lilly) or 5-FU, two widely used nucleoside analogs, in delaying the onset and growth of liver metastasis. Cyclacel has initiated a number of clinical trials to evaluate sapacitabine in both solid and hematological tumors laying the foundation for future Phase 2 studies and combination studies with other anti-cancer agents. Three Phase 1 studies have been completed, which evaluated safety and pharmacokinetics of a variety of dosing schedules in approximately 120 patients with solid tumors. Sapacitabine is currently being evaluated in two Phase 2 trials in patients with advanced cutaneous T-cell lymphoma (CTCL) and in elderly patients with acute myeloid leukemias (AML).  See http://www.cyclacel.com/cyc/rd/programs/oncology/sapacitabine/ .