PF-04802367 (PF-367) 是一种高选择性 GSK-3 抑制剂，对 GSK-3β 酶的 IC₅₀ 为 2.1 nM。PF-04802367 具有理想的中枢神经系统 (CNS) 特性和效力。PF-04802367 抑制两种 GSK-3 亚型（GSK-3α 和 GSK-3β）效果差不多， IC₅₀ 值分别为 10.0 和 9.0 nM。

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.

Solid

GSK-3α 10 nM (IC50) GSK-3β 9 nM (IC50

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 (t1/2=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 IC50 of 466 nM.
PF-367 has good cell viability (IC50 of 117 μM in THLE cytotoxicity assays) and an IC50 >100 μM in a hERG screening assay.
PF-367 shows significant right shifts against β-catenin translocation in HeLa cells with EC50 of 6.2 μM, gene transcription in U20S cells with EC50 of 20.6 μM, and cell proliferation in HeLa cells as evaluated

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. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Steven H Liang, et al. Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging. Angew Chem Int Ed Engl. 2016 Aug 8;55(33):9601-5.
[2]. Vadim Bernard-Gauthier, et al. Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery. J Med Chem. 2019 Nov 14;62(21):9600-9617.

In Vitro: DMSO : 100 mg/mL (276.41 mM; Need ultrasonic)配制储备液