Physicochemical Properties
| CAS # | 2821803-61-4 |
| Appearance | Light yellow to green yellow 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 | CDK4 CDK6 |
| ln Vitro | Compound 26 (HEMTAC CDK4/6 degrader 1; 0.01-1 μM; 24 h) causes CDK4 and CDK6 degradation in treated B16F10 cells with Dmax (highest degradation percentage) of 88% and 92%, respectively, and DC50 values (drug concentration that promotes 50% protein degradation) of about 26 and 19 nM[1]. A range of human cancer cell lines are resistant to the anti-proliferative effects of HEMTAC CDK4/6 degrader 1 (0.01-100 μM; 72 h) [1]. In B16F10 cells, HEMTAC CDK4/6 degrader 1 (250 nM; 24 or 48 h) dose-dependently promotes apoptosis and stops the cell cycle in the G0/G1 phase [1]. |
| ln Vivo | In C57BL/6J mice with B16F10 melanoma xenografts, HEMTAC CDK4/6 degrader 1 (compound 26; 20 and 40 mg/kg; ip; once daily for 15 days) exhibits antitumor efficaciousness [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: B16F10, A375, HepG2, MDA-MB-231, and A549 cells Tested Concentrations: 0.01-100 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited cell growth in a dose-dependent manner. Apoptosis Analysis[1] Cell Types: B16F10 cells Tested Concentrations: 250 nM Incubation Duration: 48 hrs (hours) Experimental Results: Induced cell apoptosis in a dose -dependent manner. Cell Cycle Analysis[1] Cell Types: B16F10 cells Tested Concentrations: 250 nM Incubation Duration: 48 hrs (hours) Experimental Results: Increased the amount of B16F10 cells in the G0/G1 phase. Western Blot Analysis[1] Cell Types: B16F10 cells Tested Concentrations: 0.01, 0.05, 0.1, 0.5, and 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced CDK4/6 degradation in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice bearing B16F10 melanoma xenografts[1] Doses: 20 and 40 mg/kg Route of Administration: intraperitoneal (ip)injection; daily, for 15 days Experimental Results: Inhibited tumor growth and resulted in fewer CDK4/6-positive cells and led to much more necrosis. |
| References |
[1]. Targeted Protein Degradation Induced by HEMTACs Based on HSP90. J Med Chem. 2023 Jan 12;66(1):733-751. |
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.) |