| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
hLigI ( IC50 = 5 μM ); hLigIV ( IC50 = 5 μM ); hLigIII ( IC50 = 9 μM )
L189 targets DNA ligase I, DNA ligase III, and DNA ligase IV. These enzymes are essential for DNA replication and repair. DNA ligase I is involved in Okazaki fragment joining during DNA replication and in base excision repair (BER). DNA ligase III is also involved in BER. DNA ligase IV is essential for non-homologous end joining (NHEJ), a pathway for repairing double-strand breaks. By inhibiting all three ligases, L189 blocks both BER and NHEJ, making cells more sensitive to DNA damage. |
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| ln Vitro |
L189 has IC50 values of 5 μM, 9 μM, and 5 μM, respectively, which means that it inhibits DNA Ligase I, III, and IV activity[1].
L189 (5 μM, 48 h) induces a cytotoxic environment that kills cells and has good anti-proliferation activity[2]. L189 (5 μM, 48 h) and TMZ both lessen HeLa nuclear staining[2]. L189 (5 μM, 48 h) improves HeLa growth arrest induced by TMZ when combined with TMZ, potentially in the G2/M cell cycle phase, without utilizing cell death mechanisms[2]. In vitro, L189 is a potent inhibitor of DNA ligase I, III, and IV with IC₅₀ values of 5 μM, 9 μM, and 5 μM, respectively. It blocks DNA binding. It significantly enhances the killing effect of ionizing radiation on HCT116 colon cancer cells and other cancer cell lines. These in vitro activities confirm its mechanism as a DNA ligase inhibitor and its ability to sensitize cancer cells to DNA damage. |
| ln Vivo |
Detailed in vivo activity data for L189 are not extensively reported in the available literature. However, as a compound that sensitizes cancer cells to DNA damage, it is expected to have in vivo efficacy in combination with DNA-damaging agents such as radiation or chemotherapeutics. Further in vivo studies would be required to fully characterize its therapeutic potential.
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| Enzyme Assay |
Non-cell-based enzyme assays for L189 typically involve in vitro DNA ligase activity assays using purified recombinant DNA ligase I, III, or IV enzymes. The compound is incubated with the enzyme, a nicked DNA substrate, and ATP at varying concentrations. DNA ligase activity is measured by quantifying the sealing of the nick using gel electrophoresis or fluorescence-based methods. IC₅₀ values of 5 μM, 9 μM, and 5 μM for ligase I, III, and IV, respectively, are determined.
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| Cell Assay |
Cell Line: HeLa cells
Concentration: 5 μM Incubation Time: 48 h Result: Blocked to HeLa growth and proliferation along with TMZ and not mark the significant cell cytotoxicity alone. Cellular assays for L189 are performed using various cancer cell lines, such as HCT116 colon cancer cells. Cells are treated with the compound in combination with ionizing radiation or DNA-damaging agents. Cell survival is assessed using clonogenic assays or standard viability assays. The compound's ability to enhance the cytotoxicity of DNA-damaging agents is quantified. |
| Animal Protocol |
In vivo animal models for L189 would be required to assess its therapeutic potential. Based on its mechanism as a DNA ligase inhibitor that sensitizes cancer cells to DNA damage, relevant models could include xenograft studies in immunodeficient mice bearing cancer cell lines, in combination with radiation or chemotherapy. The compound would be administered via appropriate routes, and tumor growth inhibition would be monitored.
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| ADME/Pharmacokinetics |
L189 has a molecular weight of 246.29 g/mol and a molecular formula of C₁₁H₁₀N₄OS. Its CAS number is 64232-83-3. The compound is supplied as a solid with a purity of >98%. It is soluble in DMSO. Storage conditions: -20°C. The compound is a DNA ligase inhibitor. Detailed pharmacokinetic parameters such as half-life and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for L189 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
L189 is a DNA ligase I, III, and IV inhibitor with IC₅₀ values of 5 μM, 9 μM, and 5 μM, respectively. It blocks DNA binding and inhibits base excision repair (BER) and non-homologous end joining (NHEJ). L189 specifically sensitizes cancer cells to DNA damage and increases the cytotoxicity of DNA-damaging agents. Its CAS number is 64232-83-3.
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| Molecular Formula |
C11H10N4OS
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|---|---|
| Molecular Weight |
246.29
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| Exact Mass |
246.057
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| Elemental Analysis |
C, 53.64; H, 4.09; N, 22.75; O, 6.50; S, 13.02
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| CAS # |
64232-83-3
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| Related CAS # |
64232-83-3
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| PubChem CID |
824710
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| Appearance |
Light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.726
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| LogP |
0.32
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
396
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=C1N([H])C(C(=C(N([H])[H])N1[H])/N=C(\[H])/C1C([H])=C([H])C([H])=C([H])C=1[H])=O
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| InChi Key |
SAKOXVNKDMWWLF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H10N4OS/c12-9-8(10(16)15-11(17)14-9)13-6-7-4-2-1-3-5-7/h1-6H,(H4,12,14,15,16,17)
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| Chemical Name |
6-amino-5-(benzylideneamino)-2-sulfanylidene-1H-pyrimidin-4-one
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| Synonyms |
L 189; L189; L-189
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~49 mg/mL (~199 mM)
Water: ˂1 mg/mL Ethanol: ˂1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0603 mL | 20.3013 mL | 40.6025 mL | |
| 5 mM | 0.8121 mL | 4.0603 mL | 8.1205 mL | |
| 10 mM | 0.4060 mL | 2.0301 mL | 4.0603 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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