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Information
GSK3A
GSK3B (Mutant:WT, C199A)
Inhibitor
up to 1 uM
In Vitro Validations
Uniprot ID: P49840
Target Class:
Kinase
Target SubClass: CMGC
Potency: INH
Potency Value: 29.5 %
Potency Assay: measured at 10 µM in Z′-LYTETM technology at ATP and peptide concentrations around their Km values
PDB ID for probe-target interaction (3D structure):
--
Potency assay (off target):
The selectivity of tideglusib was assessed in a panel of 68 kinases at 10 µM. Percent inhibition observed for TAK1-TAB1 (93.5%), KDR (99.77 %), MAPKAPK2 (96.90 %), JAK3 (86.67 %), Aurora A (87.64 %)
Tideglusib significantly reduced cell proliferation, viability, and migration of the neuroblastoma cells at 25 micro-molar concentration (PMID: 33030673) but can promote cell proliferation and wound healing in other cell types (PMID: 36831078, PMID: 35729652). At higher doses, off-target activity towards Pif1 (PMID: 36092604) may occur.
(last updated:
24 Apr 2024 )
SERP
Ratings
In Cell Rating
SERP
Comments:
This is a reported inhibitor of GSK3beta with an irreversible, non-competitive mechanism of action. Despite careful mechanistic work (Domínguez et al 2011) the exact mechanism of inhibition is unclear leaving the possibility that this compound is acting through an interference-type mechanism. Moreover, this compound was found to inhibit ca. 25% of tested kinases by >50% at 10 uM making in of limited value as a tool compound for understanding GSK3beta biology. Whilst there is considerable cellular and in vivo data with this compound it is hard to be confident that this can be clearly linked back to inhibition of GSK3beta.
(last updated:
30 Apr 2024 )
SERP+
Ratings
In Cell Rating
SERP+
Comments:
Tideglusib is a potent GSK-3beta inhibitor but, based on the provided data, clearly lacks selectivity on screened off-target kinases at 10 µM. Additional testing on other off-target kinases as well as non-kinase off-targets at lower concentrations, with respect to the compound's high potency would be necessary. Furthermore, determination of k(inact)/K(I) would be more meaningful to describe the potency of this functionally irreversible inhibitor.
Despite promising in vivo data, there is no evidence provided on cellular engagement with the target GSK-3beta.
