CHIR98014

CHIR98014 is a reversible, cell-permeable activator of the WNT pathway, through inhibition of both isoforms of glycogen synthase kinase 3 (GSK3α and GSK3β) with IC₅₀ values of 0.65 and 0.58 nM, respectively. It shows at least 500-fold selectivity for GSK-3 versus 20 other serine/threonine or tyrosine kinases (Ring et al.).

DIFFERENTIATION

• Induces differentiation of endothelial progenitor cells from human induced pluripotent stem cells in the absence of VEGF (Lian et al.).
• Enhances osteogenic-like differentiation of rat mesenchymal stem cells cultured with high phosphate, including BMP-2 expression, calcium deposition, and alkaline phosphatase activity (Guerrero et al.).

METABOLISM

• Activates glycogen synthase in cells, lowers blood glucose levels and improves glucose disposal in insulin-resistant rats and diabetic db/db mice (Ring et al.).

DISEASE MODELING

• Reduces tau phosphorylation in the cortex and hippocampus of postnatal rat brains, which is implicated in the formation of neurofibrillary tangles and defects in axonal transport in Alzheimer's disease (Selenica et al.).