Physicochemical Properties
| CAS # | 2378780-25-5 |
| PubChem CID | 141755738 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 35 |
| Complexity | 667 |
| Defined Atom Stereocenter Count | 0 |
| 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 | Nur77[1] |
| ln Vitro | Nur77 antagonist 1 (Compound ja) exhibits selectivity towards tumor cells from various tissues when compared to human normal breast cell lines (MCF-10A has an IC50 of 48.01 ± 2.86). Additionally, compound ja exhibits highly selective anti-proliferative activity towards all TNBC cell lines tested, including MDA-MB -231, HCC-1806, and BT549 (IC50s of 0.40 ± 0.03, 0.38 ± 0.08, and 2.12 ± 0.15, respectively). In MDA-MB-231-sictr cells, Nur77 antagonist 1 (0-2 μM, 6 h) causes apoptosis in a Nur77-dependent way [1]. In MDA-MB-231 cells, Nur77 antagonist 1 (0-5 μM, 6 h) mediates the TP53 phosphorylation pathway, resulting in Nur77-dependent cell cycle arrest and apoptosis [1]. |
| ln Vivo | In the MDA-MB-231 xenograft nude mice model of breast cancer, Nur77 antagonist 1 (Compound ja) (10 mg/kg, intraperitoneal injection) has strong anti-tumor activity and good in vivo tolerance [1]. In zebrafish embryo models, Nur77 antagonist 1 (1.25-5 μM) exhibits an excellent in vivo safety profile [1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 0-5 μM Incubation Duration: 6 h Experimental Results: Induced extrinsic Nur77 degradation. Induced PARP cleavage in a dose- and time-dependent manner in MDA-MB- 231 cells. Apoptosis Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 0.32-5 μM Incubation Duration: 5 h Experimental Results: demonstrated the apoptotic cells accounted for 15.10, 25.38, 40.01, 54.83, and 74.62% at 0.32, 0.63, 1.25, 2.5, and 5.0 μM. |
| Animal Protocol |
Animal/Disease Models: the breast cancer MDA-MB-231 xenograft nude mice model[1] Doses: 10 mg/kg Route of Administration: ip Experimental Results: decreased tumor weight and volume with tumor growth inhibition (TGI) of 99.95%. Increased cleaved caspase 3 and diminished the proliferation marker Ki67 expression in tumor tissues. |
| References |
[1]. Discovery of 5-(Pyrimidin-2-ylamino)-1H-indole-2-carboxamide Derivatives as Nur77 Modulators with Selective and Potent Activity Against Triple-Negative Breast Cancer. J Med Chem. 2023 Nov 20. |
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.) |