GS-444217

1262041-49-5

C23H21N7O

DMSO : 15.5 mg/mL (37.67 mM; Need ultrasonic and warming)

MAPK/ERK Pathway

GS-444217 is a potent and selective ATP-competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with an IC₅₀ of 2.87 nM^[1]. IC50 & Target: ASK1^[1] In Vitro: Treatment with GS-444217 reduces ASK1 phosphorylation and prevents the phosphorylation of MKK3/6, MKK4, p38, and JNK at concentrations of 0.3 uM and above with full suppression of ASK1 activity at 1 uM. GS-444217 (1 uM) reduces ASK1 activity within 5 minutes of addition to the cultures, reaching a maximum level of inhibition by 30 minutes. Removal of GS-444217 from the cultures results in reactivation of ASK1 autophosphorylation within 10 minutes and near-complete recovery 2 hours after drug washout^[1]. In Vivo: GS-444217 reduces oxidative stress (OS)-induced ASK1 signaling in kidney and inhibits acute renal tubular injury in rats. GS-444217 (30 mg/kg) inhibits activation of ASK1, p38, and JNK in rat kidney. GS-444217 has an in vivo EC₅₀ of approximately 1.6 uM for inhibiting the ASK1 pathway in rodent kidney^[1].