PF-04802367

PF-04802367 (PF-367) is a highly selective GSK-3 inhibitor with an IC 50 of 2.1 nM based on a recombinant human GSK-3β enzyme assay and 1.1 nM based on ADP-Glo assay. PF-04802367 shows desirable central nervous system (CNS) properties and potency. PF-04802367 is equally effective at inhibition of the two known GSK-3 isoforms ( GSK-3α and GSK-3β ) with IC 50 values of 10.0 and 9.0 nM in mobility shift assays, respectively

In Vitro

PF-04802367 (PF-367) is efficient at inhibiting GSK-3β enzymatic activity in vitro with ligand and lipophilic efficiency scores of 0.46 and 7.0, respectively. PF-367 has reasonable in vitro stability in human hepatic microsomes (t 1/2 =78.7 min), has excellent passive permeability. In a stable inducible CHO cell line over-expressing GSK-3β and its substrate tau, PF-367 inhibited phosphorylation of tau with an IC 50 of 466 nM. PF-367 has good cell viability (IC 50 of 117 μM in THLE cytotoxicity assays) and an IC 50 >100 μM in a hERG screening assay. PF-367 shows significant right shifts against β-catenin translocation in HeLa cells with EC 50 of 6.2 μM, gene transcription in U20S cells with EC 50 of 20.6 μM, and cell proliferation in HeLa cells as evaluated by Ki-67 incorporation with EC 50 of 9.0 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

PF-04802367 (PF-367) a potent GSK-3 inhibitor with exceptional kinome selectivity that modulates phosphorylated tau levels in vivo. Inhibition of phosphorylation of tau in brain by PF-367 (A single subcutaneous of 1, 3.2, 10, 32 or 50 mg/kg) is dose-dependent . PF-04802367 (PF-367), a potent type-I dual GSK-3α/β inhibitor, showing promising absorption; distribution, metabolism and elimination (ADME) properties combined with robust CNS/peripheral p-Tau and muscle phosphorylated glycogen synthase (pGS) inhibition in vivo. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Sprague-Dawley rats Dosage: 1, 3.2, 10, 32 or 50 mg/kg Administration: A single subcutaneous Result: Inhibition of phosphorylation of tau in brain is dose-dependent.

Form:Solid

IC50& Target:GSK-3α 10 nM (IC 50 ) GSK-3β 9 nM (IC 50 )