scd1 in hepg2 cell

XEN723 is a potent thiazolylimidazolidinone Stearoyl-CoA Desaturase (SCD1) inhibitor(IC50s of 45 and 524 nM in mouse and HepG2 cell, respectively).

MK-8245 trifluoroacetate is a phenoxy piperidine isoxazole derivative functioning as a potent, liver-targeting stearoyl-CoA desaturase (SCD) inhibitor, demonstrating significant anti-diabetic and anti-dyslipidemic effects. It showcases high specificity and efficacy against SCD1 across various species, with IC50 values of 1 nM for human SCD1 and 3 nM for both rat and mouse SCD1. MK-8245's mechanism includes a tetrazole acetic acid moiety that facilitates liver-targeting through OATPs recognition. Its inhibition potency in rat hepatocyte assays (IC50 of 68 nM) surpasses that in HepG2 cell assays devoid of active OATPs (IC50 of ~1 μM), highlighting its liver specificity. Moreover, MK-8245 exhibits over 100,000-fold selectivity against Δ-5 and Δ-6 desaturases in comparative assays. In vivo studies reveal MK-8245's preferential liver distribution in mice, rats, dogs, and rhesus monkeys, underscoring its potential for minimizing adverse effects in non-target tissues. Additionally, its administration in eDIO mice before glucose challenges significantly improves glucose clearance, indicating its therapeutic promise in diabetes management.

Agrimonolide, a compound derived from isocoumarins and found mainly in the herb Agrimonia pilosa Ledeb, has significant biological activity. agrimonolide exerts anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced activation of JAK-STATs and p38 MAPKs signaling pathways. Agrimonolide and its derivative, desmethyl agonolide, have been shown to be effective in increasing insulin-mediated glycogen levels in hepatocytes and may play a key role in regulating insulin-resistant HepG2 cells. agrimonolide exhibits inhibitory effects on cancer progression and induction of cell death and apoptosis by targeting SCD1 in ovarian cancer cells. In particular, Agrimonolide exhibited a dose-dependent inhibition of proliferation, migration and invasion of A2780 and SKOV-3 cells, while promoting apoptosis. The compound was also found to induce iron-mediated cell death while increasing reactive oxygen species (ROS) and total iron levels.Agrimonolide readily crosses the blood-brain barrier, suggesting its potential for therapeutic applications in neurological disorders.