SBI-477 is a chemical probe stimulated insulin signaling by deactivating the transcription factor MondoA , leading to reduced expression of the insulin pathway suppressors thioredoxin-interacting protein (TXNIP) and arrestin domain–containing 4 (ARRDC4). SBI-477 coordinately inhibits triacylglyceride (TAG) synthesis and enhances basal glucose uptake in human skeletal myocytes.