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PF-367

PF-367 : Inhibitor of GSK3A, GSK3B

Structure

Information

  • GSK3A
  • GSK3B
  • Inhibitor
  • up to 5 uM

In Vitro Validations

Uniprot ID: P49840
Target Class: Kinase
Target SubClass: CMGC
Potency: IC50
Potency Value: 10 nM
Potency Assay: Mobility shift assay
PDB ID for probe-target interaction (3D structure): 5K5N
Target aliases:
Glycogen synthase kinase-3 alpha, GSK3A, GSK3A_HUM ...

DOI Reference: 10.1002/anie.201603797

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): PF-367 was screened against a broad panel of 240 kinases in biochemical functional assays at a concentration of 10 μm. Only 6 kinases (including GSK-3α/β) out of 240 showed more than 65 % inhibition at this concentration. PF-367 was further profiled against a comprehensive DiscoverRx kinome panel of 386 unique kinases (442 total) that relies on competitive displacement of known probes from kinase ATP site (ca. 75 % of the kinome). PF-367 crossed over to 18 kinases (including GSK-3α/β) with more than 65 % inhibition. PF-367 has greater than 1000-fold selective for GSK-3α/β over CDK2. PF-367 exhibited greater than 450-fold selectivity for GSK-3α/β over all kinases tested and is one of the most selective ATP-competitive kinase inhibitors reported.
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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

The compound is effective at inhibiting tau phosphorylation in rat brain. However, "the short in vivo half-life of PF-367 precluded any long-term chronic behavioral studies and kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent."

(last updated: 7 Feb 2023 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 21 Feb 2023 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Rat is a suitable in vivo model, but the short in vivo half-life of PF-367 will prevent long-term chronic studies

(last updated: 27 Feb 2023 )