L189 is a DNA ligase I, III and IV inhibitor (IC50 are 5, 9 and 5 μM respectively) that blocks DNA binding. L189 prevents non-homologous end joining (NHEJ) and base excision repair (BER). L189 increases the cytotoxicity of agents that damage DNA and specifically makes cancer cells more susceptible to DNA damage. L189 will serve as a lead compound for the development of anticancer agents in addition to offering insights into the cellular function of these enzymes.
Physicochemical Properties
| Molecular Formula | C11H10N4OS |
| Molecular Weight | 246.29 |
| Exact Mass | 246.057 |
| Elemental Analysis | C, 53.64; H, 4.09; N, 22.75; O, 6.50; S, 13.02 |
| CAS # | 64232-83-3 |
| Related CAS # | 64232-83-3 |
| PubChem CID | 824710 |
| Appearance | Light yellow solid powder |
| Density | 1.5±0.1 g/cm3 |
| Index of Refraction | 1.726 |
| LogP | 0.32 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 17 |
| Complexity | 396 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | SAKOXVNKDMWWLF-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 6-amino-5-(benzylideneamino)-2-sulfanylidene-1H-pyrimidin-4-one |
| Synonyms | L 189; L189; L-189 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | hLigI ( IC50 = 5 μM ); hLigIV ( IC50 = 5 μM ); hLigIII ( IC50 = 9 μM ) |
| 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]. |
| 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. |
| References |
[1]. Rational Design of Human DNA Ligase Inhibitors that Target Cellular DNA Replication and Repair. Cancer Res 2008; 68: (9). May 1, 2008. [2]. Combinatorial Use of DNA Ligase Inhibitor L189 and Temozolomide Potentiates Cell Growth Arrest in HeLa. Current Cancer Therapy Reviews, 2018, 14, 1-11. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~49 mg/mL (~199 mM) Water: ˂1 mg/mL Ethanol: ˂1 mg/mL |
| 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 |