Physicochemical Properties
| Molecular Formula | C27H27F2N9O4S |
| Molecular Weight | 611.62 |
| CAS # | 2891692-83-2 |
| 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 | PI3Kα 0.06 nM (IC50) mTOR 3.12 nM (IC50) |
| ln Vitro | Compound 48, also known as PI3K/mTOR Inhibitor-12, has been shown to suppress the proliferation of cancer cells. For PC-3, HT-29, HCT116, LOVO, and HUVEC cells, its IC50 values are 0.07, 0.09, 0.54, 0.54, and 0.68 μM, respectively [1]. In HCT116 and HT-29 cells, PI3K/mTOR Inhibitor-12 (0.25-1 μM; 12-48 h) suppresses PI3K and mTOR activation within the cellular context[1]. |
| ln Vivo | In female BALB/c nude mice, PI3K/mTOR Inhibitor-12 (compound 48; 20 mg/kg; po; daily, for 14 d) reduces the formation of HCT116 xenograft tumors[1]. Male SD rats administered with 1 or 5 mg/kg of PI3K/mTOR Inhibitor-12 via IV or PO showed quick plasma clearance (1428 mL/h/kg), a short half-life (2.33 h), and an AUC0-∞ of 1356 h*ng/mL[1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: HCT116 and HT-29 cells Tested Concentrations: 0.25, 0.5, and 1 μM Incubation Duration: 12, 24, and 48 hrs (hours) Experimental Results: Inhibited the expression levels of AKT, p70S6K and their phosphorylated forms in a dose- and time-dependent manner . |
| Animal Protocol |
Animal/Disease Models: HCT116 xenografts in female BALB/c nude mice[1] Doses: 20 mg/kg Route of Administration: Oral administration, daily, for 14 days Experimental Results: decreased the growth of HCT116 tumors, and the tumor growth inhibition (TGI) was 73.33%. Had lower liver toxicity of HCT116 xenografts in female BALB/c nude mice. Animal/Disease Models: Male SD rats[1] Doses: 1 and 5 mg/kg Route of Administration: intravenous (iv) injection (1 mg/kg) and oral administration (5 mg/ kg) Experimental Results: 1.19 Parameter IV (1 mg/kg) Parameter PO (5 mg/kg) T1/2 (h) 0.6 T1/2 (h) 2.33 CL (mL/h/kg) 1428 Cmax (ng/mL) 1218 Vdss (mL/Kg) 528 AUC0-∞ (h*ng/mL) 1356 AUC0-∞ (h*ng/mL) 760 F% 33.1 |
| References |
[1]. Function-oriented synthesis of Imidazo[1,2-a]pyrazine and Imidazo[1,2-b]pyridazine derivatives as potent PI3K/mTOR dual inhibitors. Eur J Med Chem. 2022 Dec 20;247:115030. |
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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6350 mL | 8.1750 mL | 16.3500 mL | |
| 5 mM | 0.3270 mL | 1.6350 mL | 3.2700 mL | |
| 10 mM | 0.1635 mL | 0.8175 mL | 1.6350 mL |