PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent and orally active pyruvate dehydrogenase kinase 4 (PDK4) inhibitor with an IC50 value of 84 nM. PDK4-IN-1 hydrochloride potently represses cellular transformation and cellular proliferation and induces apoptosis. PDK4-IN-1 hydrochloride has antidiabetic, anticancer and anti-allergic activity.

Product information

CAS Number: 2310262-11-2

Molecular Weight: 393.87

Formula: C22H20ClN3O2

Chemical Name: 1-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-9, 10-dihydroanthracene-9, 10-dione hydrochloride

Smiles: Cl.O=C1C2=CC=CC(=C2C(=O)C2=CC=CC=C12)C1C=NN(C=1)C1CCNCC1

InChiKey: ZIMLKZKPNALXKK-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 125 mg/mL (317.36 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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[1]. 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.

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.

References:

1. Lee D, et al. 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.

Products are for research use only. Not for human use.