Physicochemical Properties
| Molecular Formula | C24H24N2O4 |
| CAS # | 2770804-74-3 |
| Appearance | Typically exists as solid at room temperature |
| 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 | Topoisomerase I Topoisomerase II PI3K |
| ln Vitro | Compound 7 (topoisomerase I/II inhibitor 3) (0-100 μM) has the ability to insert into DNA, alter its topology, and partially damage DNA[1]. Topoisomerase I/II inhibitor 3 (0–4 μM, 24 h) suppresses the proliferation of HCC (hepatocellular carcinoma) cells in a dose-dependent manner. It also suppresses the migration and invasion of HuH7 and LM9 cells by preventing MMP-9 expression[1]. In LM9 and HuH7 cells, topoisomerase I/II inhibitor 3 (0-14 μM, 48 h) significantly causes apoptosis. It also dose-dependently causes mitochondrial malfunction and ROS explosion[1]. Topoisomerase I/II inhibitor 3 (0-7 μM, 48 h) suppresses the phosphorylation of the PI3K/Akt/mTOR signaling pathway and increases the expression of proteins linked to mitochondria-dependent apoptosis, including Bax, cytochrome C, cleaved-caspase-3, and cleaved-caspase-9[1]. It also decreases the expression of the inhibitory factor Bcl-2. |
| ln Vivo | Topoisomerase I/II inhibitor 3 (compound 7) (male Kunming mice, 0-400 mg/kg, IP, once) has an LD50 of 250–400 mg/kg, which results in the death of the mice in the 400 mg/kg group[1]. |
| Cell Assay |
Cell Proliferation Assay Cell Types: HCC cells (HuH7 and LM9)[1] Tested Concentrations: 0, 0.5, 1, 2, and 4 μM Incubation Duration: 24 h Experimental Results: Inhibited HCC cells proliferation in a dose-dependent manner, with IC50 values of 2.10 μM (LM9) and 1.93 μM (HuH7), respectively, and dose-dependently inhibited the formation of cell colonies. Apoptosis Analysis Cell Types: LM9 and HuH7 cells[1] Tested Concentrations: 0, 1.8, 3.5, 7, and 14 μM Incubation Duration: 48 h Experimental Results: Dramatically induced the apoptosis of LM9 and HuH7 cells in a concentration-dependent manner. Western Blot Analysis Cell Types: LM9 and HuH7 cells[1] Tested Concentrations: 0, 1.8, 3.5, and 7 μM Incubation Duration: 48 h Experimental Results: diminished the expression of the inhibitory factor Bcl-2 and promoted the expression of mitochondria-dependent apoptosis-related proteins such as Bax, cytochrome C, cleaved-caspase-3 and cleaved-caspase-9; inhibited the Phosphorylation of PI3K/Akt/mTOR signaling pathway. |
| Animal Protocol |
Animal/Disease Models: Male Kunming mice (19-22 mg, 8 mice, 4 groups)[1] Doses: 200, 250, 400 mg/kg (dissolved in 5% DMSO and castor oil) Route of Administration: IP, once Experimental Results: Did not cause the mice in the 250 mg/kg and 200 mg/kg groups to die after 2 weeks of administration, and caused the mice in the 400 mg/kg group to die, with the LD50 between 250 and 400 mg/kg. |
| References |
[1]. Design, synthesis and biological evaluation of 3-arylisoquinoline derivatives as topoisomerase I and II dual inhibitors for the therapy of liver cancer. Eur J Med Chem. 2022;237:114376. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |