EHT 5372

EHT 5372 is a strong inhibitor of DYRK’s family kinases, with IC50s of 0.22, 0.28 nM for DYRK1A and DYRK1B, respectively.

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> DYRK

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Research Areas >> Neurological Disease

CLK1:22.8 nM (IC50)

Clk2:88.8 nM (IC50)

Clk4:59 nM (IC50)

GSK3α:7.44 nM (IC50)

GSK3β:221 nM (IC50)

DYRK1A:0.22 nM (IC50)

DYRK1B:0.28 nM (IC50)

DYRK2:10.8 nM (IC50)

DYRK3:93.2 nM (IC50)

EHT 5372 is a strong inhibitor of DYRK’s family kinases, with IC50s of 0.22, 0.28 nM for DYRK1A and DYRK1B, respectively[1][2]. IC50 for DYRK2 and DYRK3 were higher (10.8 and 93.2 nM, respectively) and there was no inhibition on DYRK4. EHT 5372 displayed minimal impact on the CDC2-like kinase (CLK) family, with more than 100x selectivity over CLK1 (CLK1: IC50=22.8 nM; CLK2: IC50=88.8 nM; CLK3: IC50>10 lM; CLK4: no inhibition) and on the glycogen synthase kinase 3 (GSK3) family (GSK3α: IC50=7.44 nM; GSK3β: IC50=221 nM). EHT 5372 inhibits the direct phosphorylation of Tau by DYRK1A. EHT 5372 also normalizes both Aβ-induced Tau phosphorylation and DYRK1A-stimulated Aβ production[2].

HEK293 cells are changed with new culture medium and treated with 0.1-10 μM DYRK1A inhibitor EHT 5372 or 0.1% DMSO as vehicle for 24 h. The kinase inhibitor is tested in at least three independent experiments performed in duplicate. Cell viability is determined using a standard assay[2].

[1]. Chaikuad A, et al. An Unusual Binding Model of the Methyl 9-Anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) Confers High Selectivity for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases. J Med Chem. 2016 Nov 23;59(22):10315-10321.

[2]. Coutadeur S, et al. A novel DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro. J Neurochem. 2015 May;133(3):440-51.

CHIR-99021 (CT99021) | Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | THZ531 | RO-3306 | Flavopiridol | SB216763 | NVP 2 | TWS119 | BAY-1143572 Racemate | Harmine | CYC-065