Physicochemical Properties
| Molecular Formula | C53H72N8O4 |
| Molecular Weight | 885.19 |
| CAS # | 2836342-69-7 |
| PubChem CID | 165437257 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 22 |
| Heavy Atom Count | 65 |
| Complexity | 1570 |
| 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 | Akt3[1]. |
| ln Vitro | With an IC50 of 0.972 µM, Akt3 degrader 1 (0.001-100 µM; 24 h) exhibits antiproliferative effects in H1975OR cells[1]. In NSCLC cell lines, Akt3 degrader 1 (1.6, 8, 40, 200, and 1000 nM; 24 h) causes Akt3 degradation via the ubiquitin proteasome-mediated proteolysis process[1]. In H1975OR cells, Akt3 degrader 1 (10, 100 nM) preferentially and dose-dependently degrades exogenous Akt3 protein that only contains the PH domain, but not the Akt3 del PH mutant[1]. By interfering with Akt3's noncatalytic activities, Akt3 degrader 1 prevents H1975OR NSCLC cells from developing osimertinib-induced resistance[1]. |
| ln Vivo | In mice, Akt3 degrader 1 (10, 20 mg/kg; ip; every 3 days for 5 weeks) significantly inhibits tumor growth (TGI), with a TGI value of almost 75%[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: H1975OR cells Tested Tested Concentrations: 0.001-100 µM Incubation Duration: 24 h Experimental Results: Inhibited growth of H1975OR cells with an IC50 of 0.972 µM. Western Blot Analysis[1] Cell Types: A549, HCC827, H1975, H1975OR, PC9, H1299, and H460 cells Tested Tested Concentrations: 1.6, 8, 40, 200, 1000 nM Incubation Duration: 24 h Experimental Results: Selectively induced Akt3 degradation in all of these cell lines in a dose-dependent manner, whereas had minimal influence on Akt1 and Akt2 protein levels. |
| Animal Protocol |
Animal/Disease Models: NOD-SCID-IL2Rg -/-(NSI) mice (H1975OR xenograft model)[1]. Doses: 10, 20 mg/kg Route of Administration: intraperitoneal (ip) administration; every 3 days for 5 weeks Experimental Results: Inhibited tumor growth without causing obvious body weight loss or other signs of toxicity. |
| References |
[1]. Discovery of Isoform-Selective Akt3 Degraders Overcoming Osimertinib-Induced Resistance in Non-Small Cell Lung Cancer Cells. J Med Chem. 2022 Oct 27;65(20):14032-14048. |
Solubility Data
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1297 mL | 5.6485 mL | 11.2970 mL | |
| 5 mM | 0.2259 mL | 1.1297 mL | 2.2594 mL | |
| 10 mM | 0.1130 mL | 0.5649 mL | 1.1297 mL |