Sapacitabine

Sapacitabine

Clinical data
ATC code	none
Identifiers
IUPAC name 1-(2-cyano-2-deoxy-β-D-arabinofuranosyl)-4-(palmitoylamino)pyrimidin-2(1H)-one
Synonyms	N-[1-[(2R,3S,4S,5R)-3-Cyano-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]hexadecanamide
CAS Number	151823-14-2 Y
PubChem CID	153970
ChemSpider	135703 N
UNII	W335P73C3L
KEGG	D09722
Chemical and physical data
Formula	C26H42N4O5
Molar mass	490.64 g/mol
3D model (JSmol)	Interactive image
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 N Key:LBGFKUUHOPIEMA-PEARBKPGSA-N N
NY (what is this?)

Sapacitabine is a drug undergoing research for potential use in chemotherapy. The company Cyclacel has developed the drug sapacitibine and hopes to reach the point of bringing it to market after clinical trials are completed.

Sapacitabine is unique in that it is an orally available nucleoside analog prodrug of CNDAC that acts through a dual mechanism. As a prodrug, it exhibits the therapeutic effect upon being metabolized; CNDAC lasts longer in the bloodstream by being metabolized from sapacitibine than by being directly administered. The compound interferes with DNA synthesis by causing single-strand DNA breaks due to CNDAC being incorporated into DNA during replication or repair, then inducing 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.

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 being evaluated as of March 2016 in three different studies; a Phase 3 trial for elderly patients with AML (acute myeloid leukemia), a Phase 2 trial for MDS (myelodysplastic syndromes), and a Phase 1 trial in combination with seliciclib for cancer treatment including hereditary ovarian and breast cancers. Thus far approximately 1,000 patients have received sapacitibine treatment in all phases of trials.