Physicochemical Properties
| Molecular Formula | C22H19N3O2 |
| Molecular Weight | 357.405164957047 |
| Exact Mass | 357.147 |
| CAS # | 2310262-10-1 |
| Related CAS # | PDK4-IN-1 hydrochloride;2310262-11-2 |
| PubChem CID | 146026196 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.8 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 27 |
| Complexity | 588 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C2C=CC=CC=2C(C2C=CC=C(C=21)C1C=NN(C=1)C1CCNCC1)=O |
| InChi Key | RUCYSQLKCYBLDW-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H19N3O2/c26-21-17-4-1-2-5-18(17)22(27)20-16(6-3-7-19(20)21)14-12-24-25(13-14)15-8-10-23-11-9-15/h1-7,12-13,15,23H,8-11H2 |
| Chemical Name | 1-(1-piperidin-4-ylpyrazol-4-yl)anthracene-9,10-dione |
| 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 | The human colon cancer cell lines HCT116 and RKO were shown to be considerably less proliferative when treated with PDK4-IN-1 (Compound 8c; 50 μM; 0-72 hours). Following PDK4-IN-1 therapy, the colony formation efficiency of RKO and HCT116 cells was markedly decreased [1]. Apoptosis is dose-dependently increased in response to treatment with PDK4-IN-1 (compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) [1]. PDK4-IN-1 (compound 8c; 10 μM; 24 hours; HEK293T cells) treatment prevents PDHE1α's Ser232, Ser293, and Ser300 from being phosphorylated [1]. Compound 8c, or 10 μM PDK4-IN-1, dramatically elevated p-Akt in AML12 cells[1]. Compound 8c, PDK4-IN-1, phosphorylated p53 at serine 15 in HCT116 and RKO cells in a dose-dependent manner. PDK4-IN-1 upregulates BAX expression while downregulating BCL-xL expression. PARP1 and caspase 3 cleavage is increased by PDK4-IN-1 [1]. |
| ln Vivo | PDK4-IN-1 (compound 8c) orally administered daily for one week to C57BL/6J mice at a dose of 100 mg/kg, dramatically enhanced glucose tolerance [1]. Compound 8c (PDK4-IN-1), when preincubated, shows absorbance values of 0.26 and 0.26 in IgE/Ag (10 μM), which is a dose-dependent inhibition of β-hexosaminidase release from IgE/antigen-activated BMMC. PDK4-IN-1 treated BMMCs at concentrations of 0.20, 0.126, and 20 μM[1]. Rat PDK4-IN-1 (compound 8c) pharmacokinetic (PK) profile was assessed. In rats, PDK4-IN-1 shows a long half-life (>7 h), high bioavailability (64%) and moderate clearance (CL of 0.69). |
| Cell Assay |
Cell viability assay [1] Cell Types: HCT116 and RKO Cell Tested Concentrations: 50 μM Incubation Duration: 0 hrs (hours), 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Dramatically inhibited the proliferation of human colon cancer cell lines HCT116 and RKO. Apoptosis analysis[1] Cell Types: HCT116 and RKO Cell Tested Concentrations: 10 μM, 25 μM, 50 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dose-dependent increase in apoptosis. Western Blot Analysis[1] Cell Types: HEK293T human embryonic kidney cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Ser232, Ser293 and Ser300 phosphorylation of PDHE1α was inhibited. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice (8 weeks old) fed with high-fat diet [1] Doses: 100 mg/kg Route of Administration: po (po (oral gavage)) daily; lasted for 1 week. Experimental Results: Glucose tolerance was Dramatically improved. |
| References |
[1]. Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases. J Med Chem. 2019 Jan 24;62(2):575-588. |
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 | 2.7979 mL | 13.9895 mL | 27.9791 mL | |
| 5 mM | 0.5596 mL | 2.7979 mL | 5.5958 mL | |
| 10 mM | 0.2798 mL | 1.3990 mL | 2.7979 mL |