PF-04802367

SKU: orb1297983

Description

PF-04802367 is a potent and selective dual inhibitor of GSK-3α and GSK-3β, exhibiting low nanomolar IC₅₀ values. Its favorable CNS properties make it a valuable research tool for investigating GSK-3's role in neurological diseases, tauopathies, and mood disorders in both cellular and animal models.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1962178-27-3
• MW: 361.78
• Purity: 98.76% (May vary between batches)
• Formula: C₁₆H₁₆ClN₅O₃
• SMILES: COc1ccc(cc1Cl)-c1ocnc1C(=O)NCCCn1cncn1
• Target: GSK-3
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (11.06 mM);DMSO:100 mg/mL (276.41 mM)

Bioactivity

• Target IC50:
  GSK-3α:10 nM (IC50)|GSK-3β:9 nM (IC50)
• In Vivo:
  PF-04802367 (PF-367) is a potent type-I dual GSK-3α/β inhibitor with exceptional kinome selectivity that modulates phosphorylated tau levels in vivo. It demonstrates dose-dependent inhibition of tau phosphorylation in the brain at subcutaneous doses of 1, 3.2, 10, 32, or 50 mg/kg. Additionally, PF-367 exhibits promising ADME properties, and robust CNS/peripheral p-Tau and muscle phosphorylated glycogen synthase (pGS) inhibition in vivo.
• In Vitro:
  PF-04802367 (PF-367) effectively inhibits GSK-3β enzymatic activity in vitro, with ligand and lipophilic efficiency scores of 0.46 and 7.0, respectively . It exhibits reasonable in vitro stability in human hepatic microsomes (t1/2=78.7 min) and has excellent passive permeability . In a stable inducible CHO cell line over-expressing GSK-3β and its substrate tau, PF-367 inhibits phosphorylation of tau with an IC50 of 466 nM . PF-367 demonstrates good cell viability (IC50 of 117 μM in THLE cytotoxicity assays) and an IC50 >100 μM in a hERG screening assay . It shows significant right shifts against β-catenin translocation in HeLa cells with an EC50 of 6.2 μM, gene transcription in U2OS cells with an EC50 of 20.6 μM, and cell proliferation in HeLa cells as evaluated by Ki-67 incorporation with an EC50 of 9.0 μM .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

tau, synthase, protein, PF367, PF-367, PF04802367, PF-04802367, PF 367, PF 04802367, phosphorylation, Alzheimer, disease, inhibit, kinase-3, neurodegenerative, neurology, Inhibitor, Glycogen synthase kinase-3, Glycogen, Glycogen synthase kinase 3, GSK3, GSK-3, GSK-3α/β

Compound Identifiers

PubChem CID

60148521