SBI-477

SBI-477 is a chemical probe that stimulates insulin signaling by deactivating the transcription factor MondoA. SBI-477 can lead 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^[1]. IC50 & Target:MondoA^[1] In Vitro:SBI-477 shows potent inhibition of TAG accumulation in rat H9c2 myocytes (EC₅₀ = 100 nM) and human skeletal myotubes (EC₅₀ = 1 μM)^[1].
SBI-477 (10 μM, 24 h) leads to a marked reduction of 18:1 species and levels of TAG and DAG species^[1].
SBI-477 markedly reduces the contribution by the de novo glycerolphosphate biosynthetic pathway (K1), and results in a shift to the monoacylglycerol reacylation pathway (K2)^[1].
SBI-477 (0.3-10 μM, 24 h) increases both basal and insulin-stimulated glucose uptake, and enhances glycogen synthesis rates in human skeletal myotubes^[1].
SBI-477 (10 μM, 16 h) inhibits glucose-stimulated Arrdc4 and Txnip and increases glucose uptake in a dose-dependent manner^[2].
In Vivo:SBI-477 (50 mg/kg, s.c., once daily for 7 days) reduces expression of TAG synthesis and lipogenic genesin both muscle and liver of C57BL/6J mice with diet-induced obesity^[1].