L189 |
Catalog No.GC12131
One-Click Copy Product Info
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inhibitor of human DNA ligases I, III and IV
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 64232-83-3
Sample solution is provided at 25 µL, 10mM.
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The chemical structure of L189 had been shown [1]. Three distinct chemical steps are involved in the formation of a new phosphodiester bond in DNA: (1) enzyme adenylylation, (2) adenylyl transfer to DNA, and (3) nick sealing [2]. L189 preferentially inhibits the second step [1]. L189 showed no inhibition even at a concentration of 100 μM to T4 DNA ligase. IC50 values for L189 to inhibit human DNA ligases I, III and IV are 5 ± 2 µM, 9 ± 2 µM and 5 ± 2 µM, respectively [1].
DNA ligase I catalyzes the ligation of single-strand breaks to complete DNA replication and repair. DNA ligase III is required for mitochondrial DNA replication and repair. DNA ligase IV is specialized for repair of nuclear double-strand breaks and is required for nonhomologous end joining and V (D) J recombination [2].
In a concentration-dependent manner, L189 reduced the viability and/or proliferation of a normal breast epithelial cell line MCF10A and the cancer cell lines HeLa, MCF7 and HCT116 established from cervical, breast and colon cancers, respectively. L189 also increase the rate of killed cells in cancer cell lines, especially HCT116 colon cancer cell lines and other cancer cell lines by ionizing radiation. But L189 did not increase the rate of killed cells in the normal cell line [1].
In vivo data and clinical trials are not yet available [3].
References:
[1]. Xi Chen, Shijun Zhong, Xiao Zhu, et al. Rational Design of Human DNA Ligase Inhibitors that Target Cellular DNA Replication and Repair. Cancer Res., 2008, 68(9): 3169-3177.
[2]. Mark R. Taylor, John A. Conrad, Daniel Wahl, et al. Kinetic Mechanism of Human DNA Ligase I Reveals Magnesium-dependent Changes in the Rate-limiting Step That Compromise Ligation Efficiency. Journal of Biological Chemistry, 2011, 286(26): 23054-23062.
[3]. Christian Jekimovs, Emma Bolderson, Amila Suraweera, et al. Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising. Frontiers in Oncology, 2014, 4: Article 86.
| Cell experiment [1]: | |
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Cell lines |
Human breast epithelial MCF10A cells, human colon cancer HCT116 cells, human cervical cancer HeLa cells, and human breast cancer MCF7 cells. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0~50 µmol/L for 6 days |
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Applications |
In a concentration-dependent manner, L189 (0~50 µmol/L) reduced the proliferation and/or viability of a normal breast epithelial cell line MCF10A and the cancer cell lines MCF7, HeLa, and HCT116 established from breast, cervical, and colon cancers, respectively. In colony-forming assays, L189 was cytotoxic. L189 also increase the rate of killed cells in cancer cell lines, especially HCT116 colon cancer cell line and other cancer cell lines by ionizing radiation. But L189 did not increase the rate of killed cells in the normal cell line. |
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References: [1] Christian Jekimovs, Emma Bolderson, Amila Suraweera, et al. Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising. Frontiers in Oncology, 2014, 4: Article 86. | |
| Cas No. | 64232-83-3 | SDF | |
| Chemical Name | (Z)-6-amino-5-(benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one | ||
| Canonical SMILES | S=C(NC1=O)NC(N)=C1/N=C\C2=CC=CC=C2 | ||
| Formula | C11H10N4OS | M.Wt | 246.29 |
| Solubility | ≥ 62.5mg/mL 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0603 mL | 20.3013 mL | 40.6025 mL |
| 5 mM | 812.1 μL | 4.0603 mL | 8.1205 mL |
| 10 mM | 406 μL | 2.0301 mL | 4.0603 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)