CNDAC is a major metabolite of oral drug sapacitabine, and a nucleoside analog.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

252.23

C₁₀H₁₂N₄O₄

135598-68-4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Liu XJ, et al. Sapacitabine, the prodrug of CNDAC, is a nucleoside analog with a unique action mechanism of inducing DNA strand breaks. hin J Cancer. 2012 Aug;31(8):373-80.

  [2]. Jagan S, et al. Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine. Adv Hematol. 2012;2012:727683.

  [3]. Liu X, et al. Homologous recombination as a resistance mechanism to replication-induced double-strand breaks caused by the antileukemia agent CNDAC. Blood. 2010 Sep 9;116(10):1737-46.

1×10⁶ primary BM and PB cells are treated with 1 μM (low), 10 μM (medium), and 100 μM (high) of ara-C or CNDAC or 0.005 μM (low), 0.05 μM (medium) and 0.5 μM (high) mitoxantrone in 24 well plates at 37°C, 5% CO₂, and 100% humidity for 4 days. Appropriate untreated controls are included. Postdrug treatment, both PB and BM non-adherent cells are washed to remove compound, replated on M2-10B4 stromal layers, and reincubated at 37°C, 5% CO₂, 100% humidity. Cells are analyzed immediately posttreatment and following 3, 7, and 31 days postdrug removal.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Liu XJ, et al. Sapacitabine, the prodrug of CNDAC, is a nucleoside analog with a unique action mechanism of inducing DNA strand breaks. hin J Cancer. 2012 Aug;31(8):373-80.

  [2]. Jagan S, et al. Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine. Adv Hematol. 2012;2012:727683.

  [3]. Liu X, et al. Homologous recombination as a resistance mechanism to replication-induced double-strand breaks caused by the antileukemia agent CNDAC. Blood. 2010 Sep 9;116(10):1737-46.