DN203316

DN203316 exhibits potent and highly selective PPARδ agonistic activity in CV-1 cells (EC₅₀ = 0.02 μM), with >400-fold selectivity over PPARα (EC₅₀ = 8 μM) and PPARγ (EC₅₀ > 10 μM), showing activity comparable to GW501516 (HY-10838)^[1][2].
DN203316 (Compound 11) demonstrates excellent in vitro ADMET properties, including good metabolic stability in human, dog, rat, and mouse liver microsomes, minimal inhibition of major CYP and UGT enzymes, high plasma protein binding, good Caco-2 permeability, and no significant hERG cardiotoxicity liability^[1].
DN203316 (12-50 μM; 24 h) does not affect viability or proliferation of Raw264.7 macrophages, indicating no cytotoxicity^[1].
DN203316 (12, 25, 50 μM; pre-treated for 2 h, then co-treated with LPS (HY-D1056) for 10-24 h) dose-dependently inhibits IKKα/β phosphorylation, suppresses NF-κB signaling, reduces NF-κB luciferase activity, decreases NO production, and downregulates pro-inflammatory cytokines TNF-α and IL-6 in Raw264.7 macrophages^[1].
DN203316 (1 μM; pre-treated for 1 h, then co-treated with cholesterol for 24 h) protects AML12 and HepG2 hepatocytes from cholesterol-induced cell death without cytotoxicity, significantly reduces lipid peroxidation (oxC11-BODIPY signal), and suppresses ferroptosis, an effect reversed by PPARδ knockdown^[2].
DN203316 (1 μM; pre-treated for 1 h, then co-treated with cholesterol for 24 h) restores xCT and GPX4 expression at both mRNA and protein levels, increases intracellular GSH levels, and activates xCT promoter activity in a PPARδ-dependent manner, which is abolished by mutation of the PPARδ-binding motif^[2].
DN203316 (1 μM; pre-treated for 1 h, then co-treated with cholesterol for 24 h) regulates gene expression in hepatocytes and HSCs, restoring antioxidant genes xCT and GPX4 in hepatocytes while suppressing fibrotic markers α-SMA, COL1A1, and fibronectin in HSCs exposed to ferroptotic hepatocyte conditioned medium^[2].
DN203316 (1 μM; pre-treated for 1 h, then co-treated with cholesterol for 24 h) attenuates inflammatory and chemotactic signaling by reducing TNF-α, IL-6, and IL-1β secretion in Kupffer cells and suppressing IL-6 and CXCL12 upregulation in HSCs^[2].
DN203316 (1 μM, pre-treated for 1 h, then co-treated with cholesterol for 24 h) inhibits release of exosomal dsDNA from ferroptotic hepatocytes and blocks activation of the STING-TBK1-IRF3 signaling pathway in HSCs; Rab27a knockdown and DNase I treatment further confirm the dependence on the exosomal dsDNA axis^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.