Physicochemical Properties
| Molecular Formula | C24H25F3N6O4S |
| Molecular Weight | 550.55 |
| Exact Mass | 550.161 |
| CAS # | 2622273-55-4 |
| PubChem CID | 162676791 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 4.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 38 |
| Complexity | 840 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | INSBBZOXHUDXOP-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H25F3N6O4S/c1-32(2)12-19(34)33-7-5-13-9-18(36-3)16(10-17(13)33)30-23-28-11-14(24(25,26)27)21(31-23)29-15-6-8-38-20(15)22(35)37-4/h6,8-11H,5,7,12H2,1-4H3,(H2,28,29,30,31) |
| Chemical Name | methyl 3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]thiophene-2-carboxylate |
| 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 | PLK1-IN-4 (Compound 31) (0-5 μM; 48 hours) has good anti-proliferative effect against HCC cells [1]. In HepG2 and HT-29 cells, PLK1-IN-4 (60 and 100 nM; 24 hours) causes aberrant spindle formation [1]. G2/M arrest is the mechanism by which PLK1-IN-4 (10-300 nM; 0-48 hours) causes cancer cell death [1]. PLK1-IN-4 (0-120 nM; 24 hours) dose-dependently raises and lowers PLK1, histone H3, and NPM phosphorylation while decreasing Cdc2 phosphorylation [1]. |
| ln Vivo | In the human, mouse, dog, and monkey species, PLK1-IN-4 shows poor metabolic stability with CLhep values of 74.3, 330.9, 61.5, and 196.5 mL/min/kg, respectively [1]. Tumor growth is dose-dependently inhibited by PLK1-IN-4 (30 mg/kg; tail vein injection; once or twice daily for 12 days) [1]. PLK1-IN-4 pharmacokinetic parameters in male ICR mice [1]. IV (5 mg/kg) C0 (ng/mL) 1790 T1/2 (h) 1.47 MRT0-inf (h) 0.808 MRT0-t (h) 0.704 AUC0-t (ng·h/mL) 767 AUC0-inf (ng·h/mL) 776 CL (mL/min/kg) 107 VdSS (L/kg) 107 |
| Cell Assay |
Cell proliferation assay Cell Types: MDA-MB-231, HeLa, HCT 116, HT-29, HepG2, SMMC7721, A549, JeKo-1, K562, Karpas299, A375, DU-145 and L02[1] Tested Concentrations: 0-5 μM Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated excellent anti-proliferative activity on HCC cells, with IC50 of 11.1 nM and 70.9 nM in HepG2 and SMMC7721 cells respectively. Cell cycle analysis Cell Types: HepG2[1] Tested Concentrations: 10, 30, 60, 100 and 300 nM Incubation Duration: 0, 12, 24, 36 and 48 hrs (hours) Experimental Results: Induction of cancer cell apoptosis through G2/M arrest. Western Blot Analysis Cell Types: HepG2[1] Tested Concentrations: 0, 10, 30, 60, 90 and 120 nM Incubation Duration: 24 hrs (hours) Experimental Results: Increased phosphorylation of PLK1, histone H3 and NPM, and diminished phosphorylation of Cdc2 in a dose-dependent manner sexual manner. |
| Animal Protocol |
Animal/Disease Models: Male nu/nu balb/c (Bagg ALBino) mouse (4-6 weeks; injected with HepG2 cells) [1] Doses: 30 mg/kg Route of Administration: Tail vein injection; once or twice (two times) daily for 12 days Experimental Results: Inhibited tumor growth in a dose-dependent manner at 30 mg/kg one time/day and 30 mg/kg twice (two times) daily doses, the tumor growth inhibition (TGI) values were 120.0% and 135.2%, respectively. Animal/Disease Models: ICR mice [1] Doses: 5 mg/kg Route of Administration: IV; single (pharmacokinetic/PK/PK analysis) Experimental Results: short half-life (T1/2) of 1.47 hrs (hrs (hours)), moderate exposure, area under the curve ( AUC0-inf) is 776 ng·h/mL, and the steady-state volume of distribution (Vdss) is 5.21 liters/kg. |
| References |
[1]. Discovery of methyl 3-((2-((1-(dimethylglycyl)-5-methoxyindolin-6-yl)amino)-5-(trifluoro-methyl) pyrimidin-4-yl)amino)thiophene-2-carboxylate as a potent and selective polo-like kinase 1 (PLK1) inhibitor for combating hepatocellular carcino. |
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 | 1.8164 mL | 9.0818 mL | 18.1637 mL | |
| 5 mM | 0.3633 mL | 1.8164 mL | 3.6327 mL | |
| 10 mM | 0.1816 mL | 0.9082 mL | 1.8164 mL |