CNDAC is a major metabolite of oral drug sapacitabine, and a nucleoside analog. In Vitro: CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway, whereas lethal DSBs are mainly repaired through homologous recombination. Deficiency in two Rad51 paralogs, Rad51D and XRCC3, greatly sensitize cells to CNDAC. The Rad51D-null cell line is approximately 50-fold more sensitive to CNDAC (IC₅₀=0.006 µM) compared to 51D1.3, the Rad51D-repleted line (IC₅₀=0.32 µM)^[1]. CNDAC shows inhibitory activity against HL-60 and THP-1 cells with IC₅₀s of 1.58 µM and 0.84 µM. CNDAC (10 μM) results in a significant drop in cell survival compared to the untreated on days 4, 7, and 14. CNDAC is more effective at reducing viability and inducing apoptosis than ara-C at equivalent concentrations in the THP-1 cell line, which is defined as displaying resistance to ara-C^[2]. CNDAC induces DSBs, which are products of replication, rather than a consequence of induction of apoptosis. CNDAC causes DNA damage, and DNA-PK and ATR are dispensable for cell survival. CNDAC exhibits potent activity against human fibroblasts deficient in ATM or transfected with an empty vector, approximately 30-fold more than cells repleted with full-length ATM cDNA, with IC₅₀s of 0.01 μM and 0.3 μM, respectively. CNDAC-induced DNA damage is repaired through the homologous recombination pathway^[3].