ZINC12409120

ZINC12409120 is a high selective ERK inhibitor. ZINC12409120 acts on disrupting FGF23:α-Klotho interaction to inhibit ERK activity with an IC50 of 5.0 μM[1].

Research Areas >> Metabolic Disease

Signaling Pathways >> MAPK/ERK Pathway >> ERK

Signaling Pathways >> Stem Cell/Wnt >> ERK

ERK:5 μM (IC50)

FGF23 induces hypophosphatemia, mediated by ternary complex formed by FGF23, the FGF receptor (FGFR), and α-Klotho[1]. ZINC12409120 (1 nM-0.1 mM; 5 h) inhibits ERK reporter activities mediated by FGF23 (1 μM), with an IC50 of 5 μM[1]. ZINC12409120 (10 μM; 5 h) specificaly inhibits ERK activity mediated by FGF23:α-Klotho instead of EGF-mediated ERK activation, and exhibits no inhibitory effect on EGFR tyrosine kinase or EGF/EGFR interaction[1]. ZINC12409120 has an half-life of 8.4 h, predicted by pkCSM64 (http://biosig.unimelb.edu.au/pkcsm/)[1]. Cell Proliferation Assay[1] Cell Line: Human embryonic kidney (HEK) 293T cells Concentration: 1 nM-0.1 mM Incubation Time: 5 hours Result: Inhibited FGF23-mediated ERK reporter activity in a dose-dependent manner, with an IC50 of 5 μM. And reduced FGF23-mediated ERK activities by 70%, as well.

[1]. Liu SH, et al. Identification of Small-Molecule Inhibitors of Fibroblast Growth Factor 23 Signaling via In Silico Hot Spot Prediction and Molecular Docking to α-Klotho. J Chem Inf Model. 2022 Jul 22.