Physicochemical Properties
| Molecular Formula | C23H23CLN4O |
| Molecular Weight | 406.907923936844 |
| Exact Mass | 406.16 |
| Elemental Analysis | C, 67.89; H, 5.70; Cl, 8.71; N, 13.77; O, 3.93 |
| CAS # | 2760612-63-1 |
| PubChem CID | 162718203 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 29 |
| Complexity | 513 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | MKWLNXUIWPRODH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H23ClN4O/c24-15-21(29)26-19-11-13-28(14-12-19)20-16-25-22(17-7-3-1-4-8-17)23(27-20)18-9-5-2-6-10-18/h1-10,16,19H,11-15H2,(H,26,29) |
| Chemical Name | 2-chloro-N-(1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl)acetamide |
| Synonyms | Skp2 inhibitor 1; Skp2 inhibitor-1; Skp2-inhibitor 1; compound 14i |
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | Skp2-Cks1 communication is disrupted by Skp2 inhibitor 1 (2.8 μM, 72 hours), with IC50 values of 4.8 μM and 7.0 μM for PC-3 and MGC-803 cells, respectively [1]. Inhibitor 1 for Skp2 (10 μM, 48 hours). causes cell arrest in the S phase, stimulates cell growth, and inhibits PC-3 and MGC-803 cell migration and proliferation [1]. |
| ln Vivo | In the NOD-SCID mouse xenograft model, Skp2 inhibitor 1 (10 mg/kg; 25 mg/kg, 50 mg/kg; intraperitoneal injection/2 days, 21 days) significantly inhibited tumor growth without obvious toxicity. Furthermore, the growth of tumors was totally inhibited by treatment with Skp2 Skp2 inhibitor 1 (50 mg/Kg/2 days) [1]. By blocking Skp2 signaling dye, Skp2 inhibitor 1 decreases the size of tumors and increases the percentage of cells in tumor tissue [1]. Xenograft model of MGC-803 cells and NOD-SCID mouse PC-3 [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: PC-3, MGC-803 Tested Concentrations: 0- 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: IC50 value for Skp2−Cks1 interaction is 2.8 μM, against PC-3 and MGC-803 The IC50 values for cells were 4.8 and 7.0 μM, respectively. Apoptosis analysis [1] Cell Types: PC-3, MGC-803 Tested Concentrations: 2.5 μM, 5 μM, 10 μM Incubation Duration: 0-48 h Experimental Results: Caused cell cycle S phase arrest in a dose-dependent manner, and Apoptosis, such as nuclear fragmentation, condensation, and cell shrinkage, is induced in a dose-dependent manner. Cell proliferation assay[1] Cell Types: PC-3, MGC-803 Tested Concentrations: 0.5 μM, 1 μM, 2 μM Incubation Duration: 10 days Experimental Results: Inhibition of colony-forming ability in a dose-dependent manner. Cell migration assay[1] Cell Types: PC-3, MGC-803 Tested Concentrations: 2.5 μM, 5 μM, 10 μM Incubation Duration: 48 h Experimental Results: Inhibition of migration in a dose-dependent manner. Cell invasion experiment [1] Cell Types: PC-3, MGC-803 Tested Concentrations: 0.5 μM, 1 μM, 2 μM Incubation time |
| Animal Protocol |
Animal/Disease Models: The xenograft models of PC-3 and MGC-803 cells in NOD-SCID (severe combined immunodeficient) mouse[1]. Doses: 10 mg/kg; 25 mg/kg, 50 mg/kg Route of Administration: intraperitoneal (ip) injection (i.p.) Experimental Results:Inhibited tumor growth without obvious toxicity, the tumor growth inhibition ratio was 55.68, 71.86, and 90.42% with 10, 25, and 50 mg/Kg/2 day, respectively. |
| References | [1]. Zhang K, et al. Discovery of Novel 1,3-Diphenylpyrazine Derivatives as Potent S-Phase Kinase-Associated Protein 2 (Skp2) Inhibitors for the Treatment of Cancer. J Med Chem. 2023 Jun 8;66(11):7221-7242. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~122.88 mM) |
| 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 | 2.4575 mL | 12.2877 mL | 24.5755 mL | |
| 5 mM | 0.4915 mL | 2.4575 mL | 4.9151 mL | |
| 10 mM | 0.2458 mL | 1.2288 mL | 2.4575 mL |