Sapacitabine

Sapacitabine

Systematic (IUPAC) name
1-(2-cyano-2-deoxy-β-D-arabinofuranosyl)-4-(palmitoylamino)pyrimidin-2(1H)-one
Identifiers
CAS Number	151823-14-2
ATC code	none
PubChem	CID 153970
ChemSpider	135703
UNII	W335P73C3L
Synonyms	N-[1-[(2R,3S,4S,5R)-3-Cyano-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]hexadecanamide
Chemical data
Formula	C26H42N4O5
Molar mass	490.64 g/mol
SMILES CCCCCCCCCCCCCCCC(=O)NC1=NC(=O)N(C=C1)[C@H]2[C@H]([C@@H]([C@H](O2)CO)O)C#N
InChI 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 Key:LBGFKUUHOPIEMA-PEARBKPGSA-N
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Sapacitabine is a drug undergoing research for potential use in chemotherapy.^[1][2]

Sapacitabine is an oral nucleoside analog prodrug that acts through a dual mechanism. The compound interferes with DNA synthesis by causing single-strand DNA breaks and induces arrest of the cell division cycle at G2 phase.

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.

Clinical trials

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).

As of February 2013 it is in a phase 3 trial for AML.^[3]

References

1. Faderl S, Gandhi V, Kantarjian HM (March 2008). "Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia". Curr. Opin. Hematol. 15 (2): 101–7. doi:10.1097/MOH.0b013e3282f46e94. PMID 18300755.
2. Serova M, Galmarini CM, Ghoul A, et al. (September 2007). "Antiproliferative effects of sapacitabine (CYC682), a novel 2'-deoxycytidine-derivative, in human cancer cells". Br. J. Cancer 97 (5): 628–36. doi:10.1038/sj.bjc.6603896. PMC 2360357. PMID 17637678.
3. Patents-re-use-with-HDIs