Physicochemical Properties
| Molecular Formula | C26H21F2N7O3 |
| Molecular Weight | 517.49 |
| 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 6.717 μM (IC50) PI3Kβ 42.04 nM (IC50) PI3Kγ 7.1 nM (IC50) PI3Kδ 0.57 nM (IC50) |
| ln Vitro | In RAW264.7 and Raji cells, IHMT-PI3K-455 (1 μM, 2 hours) suppresses PI3Kγ/δ-mediated AKT phosphorylation [1]. M2 macrophages generated from THP-1 and BMDM cells have their polarization changed by IHMT-PI3K-455 (1 μM, 72 hours) [1]. |
| ln Vivo | In the MC38 tumor xenograft model, IHMT-PI3K-455 (40 mg/kg orally; once daily for 30 days) reduces tumor development [1]. By attracting and activating more CD8+ killer T cells, IHMT-PI3K-455 (40 mg/kg, oral; once daily for 30 days) suppresses the growth of tumors [1]. Sprague-Dawley rats' pharmacokinetic characteristics for IHMT-PI3K-455[1] Dosage (g/kg) route of administration Cmax in ng/mL Tmax in hours AUC0-∞ (h⋅ng/mL) T1/2 (hour) CL in terms of L/h/kg Vz = L/kg F (%) 10 po 157 3.42 838 2.71 14.76 56.02 17.6 – 1 iv 1233 0.03 477 1.59 2.12 4.80 |
| Cell Assay |
Cell Differentiation Assay[1] Cell Types: Macrophages Tested Concentrations: 0.1, 1 μM Incubation Duration: 72 h Experimental Results: Increased the proinflammatory M1 macrophage phenotype in a dose-dependent manner, with a concomitant dose-dependent decrease of the anti-inflammatory M2 macrophage phenotype. Repolarized M2 phenotype toward M1 phenotype in THP-1 and BMDM macrophages. Western Blot Analysis[1] Cell Types: RAW264.7 cells; Raji cells Tested Concentrations: 0, 0.01, 0.03, 0.1, 0.3, 1 μM Incubation Duration: 2 h Experimental Results: Potently inhibited the PI3Kγ-mediated AKT473 phosphorylation in RAW264.7 cells (human C5a stimulation) with an IC50 value of 0.015 μM. Potently inhibited the PI3Kδ-mediated AKT473 phosphorylation in Raji cells (anti-IgM stimulation) with an IC50 value of 0.010 μM. |
| Animal Protocol |
Animal/Disease Models: MC38 tumor model[1] Doses: 10 mg/ kg, 40 mg/kg Route of Administration: po (oral gavage); one time/day for 30 days Experimental Results: Dramatically inhibited tumor size in a dose-dependent manner. Increased tumor-infiltrating CD8+T cells. |
| References |
[1]. Discovery of Pyrazolo[1,5-a]pyrimidine derivative as a potent and selective PI3Kγ/δ dual inhibitor. Eur J Med Chem. 2023 Nov 15;260:115768. |
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 | 1.9324 mL | 9.6620 mL | 19.3240 mL | |
| 5 mM | 0.3865 mL | 1.9324 mL | 3.8648 mL | |
| 10 mM | 0.1932 mL | 0.9662 mL | 1.9324 mL |