| Hazard Information | Back Directory | [Biological Activity]
PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent, orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with IC50 of 84 nM. It effectively inhibits cell transformation and cell proliferation and induces apoptosis. It has antidiabetic, anticancer and antiallergic effects. | [in vitro]
PDK4-IN-1 (Compound 8c; 50 μM; 0-72 hours; HCT116 and RKO cells) treatment significantly impedes the proliferation of human colon cancer cell lines, HCT116 and RKO. The colony formation efficiency in HCT116 and RKO cells Is significantly reduced after treatment of PDK4-IN-1.
PDK4-IN-1 (Compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) treatment dose-dependently increased apoptosis.
PDK4-IN-1 (Compound 8c; 10 μM; 24 hours; HEK293T cells) treatment inhibits phosphorylation of Ser 232 , Ser 293 , and Ser 300 of PDHE1α.
10 μM of PDK4-IN-1 (Compound 8c) significantly increased p-Akt in AML12 cells.
PDK4-IN-1 (compound 8c)-induced phosphorylation of p53 on serine 15 is a dose-dependent response in both HCT116 and RKO cells. PDK4-IN-1 decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1. Cell Viability Assay | Cell Line: | HCT116 and RKO cells | | Concentration: | 50 μM | | Incubation Time: | 0 hour, 24 hours, 48 hours, 72hours | td> | Result: | Significantly impeded the proliferation of human colon cancer cell lines, HCT116 and RKO. | Apoptosis Analysis | Cell Line: | HCT116 and RKO cells | | Concentration: | 10 μM, 25 μM, 50 μM | | Incubation Time: | < td class="col2"> 24 hours | Result: | Dose-depend ently increased apoptosis. | Western Blot Analysis < /p> | Cell Line: | HEK293T human embryonic kidney cells | | Concentration: | 10 μM | | Incubation Time: < /td> | 24 hours | | Result: | Inhibited phosphorylation of Ser 232 , Ser 293 , and Ser 300 of PDHE1α. | | [in vivo]
PDK4-IN-1 (Compound 8c; 100 mg/kg; oral administration; daily; for 1 week; C57BL/6J mice) treatment significantly improves glucose tolerance.
Pre-incubation with it (compound 8c) dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs, showing that the absorbance values are 0.26, 0.20, and 0.126 in IgE/Ag, 10 μM, and 20 μM PDK4- IN-1-treated BMMCs.
The pharmacokinetic (PK) profiles of PDK4-IN-1 (compound 8c) are evaluated in rat. PDK4-IN-1 shows good bioavailability (64%), long half-life ( >7 h), and moderate clearance (CL of 0.69) in rats. | Animal Model: | C57BL/6J mice (8 -week old) fed with high-fat diet | | Dosage: | 100 mg/kg | td> | Administration: | Oral adminis tration; daily; for 1 week | | Result: | Significantly improved glucose tolerance. | | [target]
IC50: 84 nM (Pyruvate dehydrogenase kinase 4 (PDK4)) |
|
| Company Name: |
MedChemExpress
|
| Tel: |
021-58955995 |
| Website: |
www.medchemexpress.com |
|