| Identification | Back Directory | [Name]
PF-04802367 | [CAS]
1962178-27-3 | [Synonyms]
PF-04802367
N-(3-(1H-1,2,4-Triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide
4-Oxazolecarboxamide, 5-(3-chloro-4-methoxyphenyl)-N-[3-(1H-1,2,4-triazol-1-yl)propyl]-
PF367,PF 367,protein,disease,Alzheimer,PF-04802367,PF-367,Glycogen synthase kinase-3,kinase-3,synthase,Inhibitor,phosphorylation,neurology,GSK-3,neurodegenerative,tau,Glycogen synthase kinase 3,PF04802367,inhibit,Glycogen,PF 04802367 | [Molecular Formula]
C16H16ClN5O3 | [MDL Number]
MFCD30146406 | [MOL File]
1962178-27-3.mol | [Molecular Weight]
361.78 |
| Hazard Information | Back Directory | [Uses]
PF-04802367 (PF-367) is a highly selective GSK-3 inhibitor with an IC50 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 IC50 values of 10.0 and 9.0 nM in mobility shift assays, respectively[1]. | [Biochem/physiol Actions]
PF-04802367 is also known as [N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide) or PF-367. It regulates tau phosphorylation in the brain. | [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[1].
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[2]. | Animal Model: | Sprague-Dawley rats[1] | | 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.
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| [IC 50]
GSK-3α: 10 nM (IC50); GSK-3β: 9 nM (IC50) | [References]
[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. DOI:10.1002/anie.201603797
[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. DOI:10.1021/acs.jmedchem.9b01030 |
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