Physicochemical Properties
| CAS # | 2770108-93-3 |
| Appearance | White to off-white solid powder |
| 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 | EZH2 EZH2 490 nM (IC50) BRD4 34 nM (IC50) |
| ln Vitro | Compound D7, YM458 (0-30 μM; 6 days) exhibits antiproliferative properties against AsPC-1 cells, with an IC50 of 0.69 ± 0.16 μM. Additionally, exposure to 1 μM for 72 hours dramatically reduces the levels of c-Myc and H3K27me3 in AsPC-1[1]. YM458 (0-30 μM; 4 or 6 days) strongly decreases the growth of A549 lung cancer cells and HCT116 colorectal cancer cells at 1 μM, as well as a variety of other solid cancer cell types[1]. AsPC-1, HCT116, and A549 cancer cell colony formation is inhibited in a dose-dependent manner by YM458 (0.05-0.4 μM; 12-20 days)[1]. |
| ln Vivo | YM458 (60 mg/kg; IP; every other day, for 38 days) inhibits the formation of tumors in AsPC-1 cells by 38.6% and in A549 cells by 62.3%[1]. Female BALB/c mice's pharmacokinetic parameters for YM458[1]. AUC0-24 (ng/mL·h) 27126.3 4383.6 IP (80 mg/kg) PO (80 mg/kg) t1/2 (h) 3.81 4.16 Tmax (h) 1 1 Cmax (ng/mL) 273220.1 13509.1 CL (mL/min/kg) 4.88 F (%) 4.94 |
| Cell Assay |
Western Blot Analysis Cell Types: AsPC-1[1] Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: diminished the degree of H3K27me3 and c-Myc Dramatically. Cell Proliferation Assay Cell Types: AsPC -1, SW1990, CFPAC-1, A549, HCC827, H1650, H292, H460, DLD1, HCT116, and RKO[1] Tested Concentrations: 0-30 μM Incubation Duration: 4 or 6 days Experimental Results: Inhibited cell proliferation on a broad range of solid cancer cells, and Dramatically suppressed proliferation of A549 lung cancer cells and HCT116 colorectal cancer cells at 1 μM. |
| Animal Protocol |
Animal/Disease Models: BALB/c nude mice (injected with A549 or AsPC-1 )[1] Doses: 60 mg/kg Route of Administration: IP; every other day, for 38 days Experimental Results: Prevented tumor growth with inhibitory rates of 38.6% in AsPC-1 cells and 62.3% in A549 cells. |
| References | [1]. Guo Z, et al. Design and Synthesis of Dual EZH2/BRD4 Inhibitors to Target Solid Tumors. J Med Chem. 2022;65(9):6573-6592. |
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.) |