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CNDAC

Catalog No.GC33177

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

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CNDAC Chemical Structure

Cas No.: 135598-68-4

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1mg
$313.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

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.

References:

[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.

Background

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].

[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.

Chemical Properties

Cas No. 135598-68-4 SDF
Canonical SMILES O=C(N=C(N)C=C1)N1[C@H]2[C@@H](C#N)[C@H](O)[C@@H](CO)O2
Formula C10H12N4O4 M.Wt 252.23
Solubility Soluble in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 3.9646 mL 19.8232 mL 39.6464 mL
5 mM 0.7929 mL 3.9646 mL 7.9293 mL
10 mM 0.3965 mL 1.9823 mL 3.9646 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 14 reference(s) in Google Scholar.)

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