Physicochemical Properties
| Molecular Formula | C22H20CLN3O2 |
| Molecular Weight | 393.866104125977 |
| Exact Mass | 393.124 |
| CAS # | 2310262-11-2 |
| Related CAS # | PDK4-IN-1;2310262-10-1 |
| PubChem CID | 146026197 |
| Appearance | Light yellow to yellow solid powder |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 28 |
| Complexity | 588 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | Cl.O=C1C2C=CC=CC=2C(C2C=CC=C(C=21)C1C=NN(C=1)C1CCNCC1)=O |
| InChi Key | ZIMLKZKPNALXKK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H19N3O2.ClH/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;1H |
| Chemical Name | 1-(1-piperidin-4-ylpyrazol-4-yl)anthracene-9,10-dione;hydrochloride |
| Synonyms | PDK4IN1 HCl; PDK4 IN 1 HCl |
| 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, avoid exposure to moisture. |
| 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 | PDK4-IN-1 (Compound 8c; 50 μM; 0-72 hours; HCT116 and RKO cells) treatment significantly hindered the proliferation of human colon cancer cell lines HCT116 and RKO. The colony formation efficiency of HCT116 and RKO cells was significantly reduced after PDK4-IN-1 treatment [1]. Treatment with PDK4-IN-1 (compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) dose-dependently increases apoptosis [1]. Treatment with PDK4-IN-1 (compound 8c; 10 μM; 24 hours; HEK293T cells) inhibits the phosphorylation of Ser232, Ser293, and Ser300 of PDHE1α [1]. 10 μM PDK4-IN-1 (compound 8c) significantly elevated p-Akt in AML12 cells[1]. PDK4-IN-1 (compound 8c) induced serine 15 phosphorylation of p53 in HCT116 and RKO cells in a dose-dependent manner. PDK4-IN-1 lowers the expression of BCL-xL and enhances the expression of BAX. PDK4-IN-1 enhances the cleavage of PARP1 and caspase 3 [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) | DMSO : ~125 mg/mL (~317.36 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: 20 mg/mL (50.78 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5389 mL | 12.6945 mL | 25.3891 mL | |
| 5 mM | 0.5078 mL | 2.5389 mL | 5.0778 mL | |
| 10 mM | 0.2539 mL | 1.2695 mL | 2.5389 mL |