CHIR-98014

CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC₅₀s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2. IC50 & Target: IC50: 0.65 nM (GSK-3α), 0.58 nM (GSK-3β)^[1] In Vitro: CHIR 98014 inhibits human GSK-3β with K_i value of 0.87 nM. CHIR 98014 causes GS stimulation in CHO-IR cells and rat hepatocytes, with EC₅₀s of 106 nM and 107 nM, respectively^[1]. CHIR-98014 (1 μM) reduces the viability of ES-CCE cells by 52%, with IC₅₀ of 1.1 μM. Moreover, CHIR-98014 in combination with CHIR-99021 results in a significant activation of the Wnt/beta-catenin pathway in ES-D3 cells. In CHIR-98014 treated cells, the T gene expression is induced up to 2,500-fold. CHIR-98014 (1 μM) also yields around 50% Brachyury-positive cells, with EC₅₀ of 0.32 μM^[2]. CHIR98014 (10 μM) prevents loss of neurites caused by 20 μM PrP1-30 in cortical and hippocampal neurons, and substantially decreases the amount of dead cells^[3]. In Vivo: CHIR 98014 (30 mg/kg, i.p.) exhibits a significant reduction in fasting hyperglycemia within 4 h of treatment and shows improved glucose disposal during an ipGTT in markedly diabetic and insulin-resistant db/db mice^[1].