CHIR-98014 is a selective GSK3 inhibitor with IC50s of 0.65 nM and 0.58 nM for GSK-3α and GSK-3β; potentiate insulin activation of glucose transport and utilization in vitro and in vivo.

Exposure of insulin receptor–expressing CHO-IR cells or primary rat hepatocytes to increasing concentrations of inhibitor CHIR 98014 resulted in a two- to threefold stimulation of the GS activity ratio above basal. The concentrations of CHIR 98014 causing half-maximal GS stimulation (EC50) were 106 nmol/l for CHO-IR cells and 107 nmol/l for rat hepatocytes. CHIR 98014 activated the GS activity ratio in isolated type 1 skeletal muscle from insulin-sensitive lean Zucker and from insulin-resistant ZDF rats. Markedly diabetic and insulin-resistant db/db mice treated with 30 mg/kg CHIR 98014 also exhibited a significant reduction in fasting hyperglycemia within 4 h of treatment and showed improved glucose disposal during an ipGTT [1]. CHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway [2].

AR-A014418

AZD1080

AZD2858

BIO

CHIR-99021

GSK-3 inhibitor 1

IM-12

LY2090314

SB 216763

SB 4152