Physicochemical Properties
| Molecular Formula | C39H40F3N7O4 |
| Molecular Weight | 727.77 |
| CAS # | 2924415-92-7 |
| PubChem CID | 170902033 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 53 |
| Complexity | 1280 |
| Defined Atom Stereocenter Count | 1 |
| 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
| ln Vitro | Compound 10zi, or Ack1 inhibitor 1, has an IC50 of 3.71 μM for 67R cells and 4.18 μM for H1975 cells, respectively, which inhibits cell growth [1]. When used alone or in conjunction with ASK120067, Ack1 inhibitor 1 (0 nM-5000 nM, 72 h) can improve the anti-tumor effect in 67R cells [1]. The phosphorylation of ACK1 and AKT in 67R cells is dose-dependently inhibited by Ack1 inhibitor 1 (1 μM and 5 μM, 6 h) [1]. |
| ln Vivo | In SD rats, a single oral dose of 10 mg/kg of Ack1 inhibitor 1 (Compound 10zi) improves the AUC value of 1920.56 h•ng/mL, Cmax of 119.52 μg/L, and oral bioavailability of 19.80%[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: 67R cells (ASK120067-resistant cells obtained from parental H1975 cells by a dose escalation method). Tested Concentrations: 0-5000 nM (combined with ASK120067) Incubation Duration: 72 h Experimental Results: Caused strong synergistic anti -growth effects on 67R cells with high synergy scores of 10.83, respectively Western Blot Analysis[1] Cell Types: 67R cells Tested Concentrations: 1 μM and 5 μM Incubation Duration: 6 h (stimulated with or without EGF for 30 min) Experimental Results: Caused moderate down-regulation of p-ACK1 and p-AKT at 1 μM. demonstrated better potency against p-AKT, while it was unable to completely inhibit p-ACK1 at 5 μM. |
| References |
[1]. Design, Synthesis, and Evaluation of (R)-8-((Tetrahydrofuran-2-yl)methyl)pyrido[2,3-d]pyrimidin-7-ones as Novel Selective ACK1 Inhibitors to Combat Acquired Resistance to the Third-Generation EGFR Inhibitor. J Med Chem. 2023 May 25;66(10):6905-6921. |
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 | 1.3741 mL | 6.8703 mL | 13.7406 mL | |
| 5 mM | 0.2748 mL | 1.3741 mL | 2.7481 mL | |
| 10 mM | 0.1374 mL | 0.6870 mL | 1.3741 mL |