Physicochemical Properties
| Molecular Formula | C18H19N3O2S |
| Molecular Weight | 341.427362680435 |
| Exact Mass | 341.119 |
| CAS # | 2118944-88-8 |
| PubChem CID | 135567026 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.6 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 24 |
| Complexity | 542 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C2=C(C(NC(C3C=C(C)C(=C(C)C=3)O)=N2)=O)C2=C1CN(C)CC2 |
| InChi Key | PXJZRFLBUBYEPV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H19N3O2S/c1-9-6-11(7-10(2)15(9)22)16-19-17(23)14-12-4-5-21(3)8-13(12)24-18(14)20-16/h6-7,22H,4-5,8H2,1-3H3,(H,19,20,23) |
| Chemical Name | 5-(4-hydroxy-3,5-dimethylphenyl)-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one |
| 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
| ln Vitro | BRD4 is selectively inhibited by FL-411. Through TR-FRET analysis, FL-411's binding affinity to the first and second bromodomains of BRD2(1), BRD4(1), and BRD4(2) was determined. The IC50 values were 24.60±0.70 μM, 0.47±0.02 μM, and 0.93±0.05 μM, respectively. FL-411 exhibited low toxicity to MCF10A cells and good BRD4(1) inhibitory activity (IC50=0.43±0.09 μM), anti-proliferative activity (MCF-7, IC50=1.62±0.06 μM; MDA-MB-231, IC50=3.27±0.14 μM), and autophagic activity (42.29% in MCF-7 cells). By inhibiting the BRD4-AMPK interaction, FL-411 causes ATG5-dependent autophagy-related cell death (ACD) in breast cancer cells by triggering the AMPK-mTOR-ULK1-regulated autophagy pathway [1]. |
| ln Vivo | Two cell line models of breast tumors, MCF-7 and MDA-MB-231, were employed as xenograft models to assess FL-411's in vivo anticancer efficacy. Three distinct FL-411 dosages were used in in vivo experiments: 25 mg/kg, 50 mg/kg, and 100 mg/kg. FL-411 demonstrated a noteworthy and dose-dependent suppression of tumor growth in every model tested; in the MCF-7 and MDA-MB-231 cell models, this inhibition was found to be 80% and 76%, respectively. In every dosage group, a noteworthy decrease in tumor weight was noted (p<0.001). Body weight was not significantly affected by FL-411 in any of the treatment groups. Tumor tissues from control and FL-411-treated mice were processed for LC3 and Ki-67 immunization Histochemical analysis in order to investigate if FL-411-mediated tumor growth suppression in vivo is linked to decreased cell proliferation and increased autophagy-related cell death. enhanced LC3 expression (p<0.001) indicated enhanced autophagy levels following FL-411 treatment, which also markedly decreased the frequency of Ki-67 (p<0.001) positive cells [1]. |
| References |
[1]. Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That InducesAMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer. J Med Chem. 2017 Dec 28;60(24):9990-10012. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~5.4 mg/mL (~15.82 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (3.66 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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. Solubility in Formulation 2: 1.25 mg/mL (3.66 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 2.9289 mL | 14.6443 mL | 29.2886 mL | |
| 5 mM | 0.5858 mL | 2.9289 mL | 5.8577 mL | |
| 10 mM | 0.2929 mL | 1.4644 mL | 2.9289 mL |