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| Targets |
L67 targets DNA ligase I and DNA ligase III, two key enzymes involved in DNA replication and repair. DNA ligase I is primarily responsible for Okazaki fragment joining during DNA replication, while DNA ligase III is involved in base excision repair (BER). As a competitive inhibitor with respect to nicked DNA, L67 binds to the DNA-binding domain of these ligases and prevents them from sealing nicks in the DNA backbone. This inhibition leads to the accumulation of DNA damage and ultimately cell death.
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| ln Vitro |
In HeLa cells, L67 (10, 15 μM; 24 hours) stimulates damage to nuclear DNA, while (0-50 μM) raises the levels of mSOX by preventing mitochondrial LigIIIα [1]. Changes in mitochondrial function caused by L67 (10 μM; 24 h) result in the induction of L67 (10, 100 μM; 24 h) in silica [1]. Caspases are activated by L67 (0-30 μM; passed in 24 hours).
In vitro, L67 is a potent inhibitor of DNA ligase I and III with IC₅₀ values of 10 μM for both enzymes. It significantly increases the cytotoxicity of DNA damaging agents. It causes nuclear DNA damage by reducing levels of mitochondrial DNA and increasing levels of mitochondrially-generated ROS. These in vitro activities confirm its mechanism as a DNA ligase inhibitor and its ability to sensitize cells to DNA damage. |
| ln Vivo |
Detailed in vivo activity data for L67 are not extensively reported in the available literature. However, as a compound that sensitizes cells to DNA damage and inhibits cell proliferation, it is expected to have in vivo efficacy in combination with DNA-damaging agents. 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 L67 typically involve in vitro DNA ligase activity assays using purified recombinant DNA ligase I or III 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 10 μM for both ligase I and III are determined.
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| Cell Assay |
Cell viability assay [1]
Cell Types: HeLa Cell Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Oxygen consumption rate (OCR) diminished by approximately 20%. Resulting in a reduction of approximately 25% in mitochondrial DNA. Apoptosis analysis [1] Cell Types: HeLa cell Tested Concentrations: 10, 100 μM Incubation Duration: 24 h Experimental Results: Experimental Results: Induced apoptosis, apoptotic cells accounted for approximately 50% of the HeLa cell population at 100 μM. Cell viability assay[1] Cell Types: HeLa Cell Tested Concentrations: 0-30 μM Incubation Duration: 24 hrs (hours) Experimental Results: Activation of caspase 1-dependent cell death pathway in cancer cells. Cellular assays for L67 are performed using various cancer cell lines. Cells are treated with the compound in combination with 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. Its effects on mitochondrial DNA levels and ROS production are measured. |
| Animal Protocol |
In vivo animal models for L67 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 |
L67 has a molecular weight of 393.48 g/mol and a molecular formula of C₂₃H₂₃N₃O₃. Its CAS number is 325970-71-6. The compound is supplied as a solid with a purity of >99%. It is soluble in DMSO. Storage conditions: -20°C. The compound is a competitive 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 L67 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 |
L67 is a novel, competitive human DNA ligase inhibitor that inhibits DNA ligase I and III with IC₅₀ values of 10 μM for both enzymes. It significantly increases the cytotoxicity of DNA damaging agents. L67 causes nuclear DNA damage by reducing mitochondrial DNA levels and increasing mitochondrial ROS. Its CAS number is 325970-71-6.
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| Molecular Formula |
C16H14BR2N4O4
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|---|---|
| Molecular Weight |
486.12
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| Exact Mass |
483.938
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| CAS # |
325970-71-6
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| PubChem CID |
135419707
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.8±0.1 g/cm3
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| Index of Refraction |
1.681
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| LogP |
6.23
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
519
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1Br)NCC(=O)N/N=C/C2=C(C=CC(=C2)[N+](=O)[O-])O)Br
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| InChi Key |
KFEPVFJQVOMODD-IFRROFPPSA-N
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| InChi Code |
InChI=1S/C16H14Br2N4O4/c1-9-13(17)5-11(6-14(9)18)19-8-16(24)21-20-7-10-4-12(22(25)26)2-3-15(10)23/h2-7,19,23H,8H2,1H3,(H,21,24)/b20-7+
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| Chemical Name |
2-(3,5-dibromo-4-methylanilino)-N-[(E)-(2-hydroxy-5-nitrophenyl)methylideneamino]acetamide
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| Synonyms |
L 67; L-67; L67
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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 : ≥ 33 mg/mL (~67.89 mM)
H2O : ~1 mg/mL (~2.06 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0571 mL | 10.2855 mL | 20.5711 mL | |
| 5 mM | 0.4114 mL | 2.0571 mL | 4.1142 mL | |
| 10 mM | 0.2057 mL | 1.0286 mL | 2.0571 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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