The properties of the principal metabolites of the oncolytic nucleoside cyclopentenylcytosine (CPEC, NSC 375,575) are being examined. In the year past, the potency of CPEC-5'-triphosphate as an inhibitor of CTP synthetase has been confirmed and the Ki established as being approximately 1 X 10(-6)M using authentic chemically synthesized nucleotide as standard. Suggestive evidence has also been obtained that CPEC-MP is subject to deamination, presumably by deoxycytidylate deaminase inasmuch as this process is nearly totally inhibited by 2'-deoxytetrahydrouridine. Evidence that CPEC-5'-diphosphate is subject to reduction, at the level of ribonucleoside-5'-diphosphate reductase has also been obtained; if confirmed, this lead would provide a route for the intracellular generation of 2'-deoxy-CPEC-5'-monophosphate. Two diester anabolites of CPEC, presumed to be CPEC-5'-diphosphocholine and diphosphoethanolamine are being synthesized as chromatographic standards and as potential substrates/inhibitors of the appropriate cytidylyl transferases and lecithin synthesizing enzymes.
