Physicochemical Properties
| Molecular Formula | C29H31N5O4S |
| Molecular Weight | 545.65 |
| CAS # | 3012609-63-8 |
| 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 | ATR 3 nM (IC50) mTOR 18 nM (IC50) ATM 100 nM (IC50) PI3Kα 100 nM (IC50) DNA-PK 662 nM (IC50) |
| ln Vitro | In a concentration-dependent manner, ATR-IN-20 (compound 48f; 0.03-3 μM; 24 hours) strongly inhibits migration in LoVo cells[1]. With IC50 values of 0.040 μM, 0.095 μM, and 0.098 μM, respectively, ATR-IN-20 (compound 48f) exhibits strong monotherapy efficacy in ATM kinase-deficient tumor cells LoVo, SW620, and OVCAR-3 cell lines[1]. In LoVo cells, ATR-IN-20 (compound 48f; 0.03-3 μM) reduces the capacity to form colonies in a dose-dependent manner[1]. Compound 48f, ATR-IN-20, has no discernible inhibition against CYP1A2, CYP2C9, or CYP2D6. Nevertheless, with IC50 values of 1 μM, ATR-IN-20 shows very modest inhibitory activity against CYP2C19 and CYP3A4[1]. |
| ln Vivo | Compound 48f, also known as ATR-IN-20, exhibits a good pharmacokinetic profile in SD rats, with a bioavailability of 30.0%, adequate plasma protein binding (PPB), high permeability, and a minimal chance of drug-drug interactions[1]. Average pharmacokinetic values of ATR-IN-20 (compound 48f) in Sprague-Dawley rats following an intravenous injection at a dose of 1 mg/kg[1]. Set of parameters Compound 48f (ATR-IN-20) T1/2 (hours) 1.32-2.45 MRT0-t (h) 1.32 MRT0-inf (h) AUC0-inf 1.36 (ng·h·mL−1) 1170 (ng·h·mL−1) AUC0-t 1160 CL (mL/kg/min/1) 14.2 Vdss (L^kg−1) 1.24 |
| Cell Assay |
Cell Migration Assay [1] Cell Types: LoVo cells Tested Concentrations: 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically inhibited migrating in a concentration -dependent manner. |
| References |
[1]. Discovery of novel 7,7-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidines as ATR inhibitors based on structure-based drug design. Eur J Med Chem. 2022 Nov 26;246:114945. |
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 | 1.8327 mL | 9.1634 mL | 18.3268 mL | |
| 5 mM | 0.3665 mL | 1.8327 mL | 3.6654 mL | |
| 10 mM | 0.1833 mL | 0.9163 mL | 1.8327 mL |