PDK4-IN-1 hydrochloride

SKU: orb1940775

Description

PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4, IC50 value = 84 nM).(In Vitro):PDK4-IN-1 hydrochloride 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 hydrochloride. In HCT116 and RKO cells, PDK4-IN-1 hydrochloride) treatment dose-dependently increased apoptosis. PDK4-IN-1 hydrochloride decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1 hydrochloride.(In Vivo):PDK4-IN-1 hydrochlorideimproved glucose tolerance in diet-induced obese mice and ameliorated allergic reactions in a passive cutaneous anaphylaxis mouse model. PDK4-IN-1 hydrochloride (C57BL/6J mice) treatment significantly improves glucose tolerance. Pre-incubation with PDK4-IN-1 (compound 8c) dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs.

Key Properties

• CAS Number: 2310262-11-2
• MW: 393.87
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₀ClN₃O₂
• SMILES: Cl.O=C1c2ccccc2C(=O)c2c(cccc12)-c1cnn(c1)C1CCNCC1
• Target: Apoptosis
• Solubility: In Vitro: DMSO : 125 mg/mL (317.36 mM)

Bioactivity

• 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 PDK4-IN-1 (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. Administration: Oral administration; daily; for 1 week. Result: Significantly improved glucose tolerance.
• 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 Ser232, Ser293, and Ser300 of PDHE1α.10 μM of PDK4-IN-1 (Compound 8c) significantly increases 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, 72 hours. 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: 24 hours. Result: Dose-dependently increased apoptosis. Western blot analysis. Cell line: HEK293T human embryonic kidney cells. Concentration: 10 μM. Incubation time: 24 hours. Result: Inhibited phosphorylation of Ser232, Ser293, and Ser300 of PDHE1α.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Apoptosis