PXS 64

PXS 64 is a mannitol-6-phosphate (M6P) analog and lipophilic prodrug of PXS 25. It effectively exerts antifibrotic effects by inhibiting the activation of latent TGF-β1. In human lung fibroblasts, PXS 64 suppresses fibrosis via the TGF-β1 pathway. It reduces the expression of TGFβ-mediated collagen IV, fibronectin, MCP-1, and phosphorylated smad2 in kidney cells while also decreasing collagen deposition in dermal scar fibroblasts. PXS 64 is applicable to research on chronic kidney disease, idiopathic pulmonary fibrosis, and scar formation.

PXS64, at a concentration of 10 µM for 48 hours, inhibits the activation of latent TGF-β1, reduces the expression of pro-fibrotic and pro-inflammatory markers, and selectively decreases TGF-β1-induced pSmad2 expression without affecting pAKT or pERK pathways. When used alone, PXS64 does not alter mRNA or protein expression of fibronectin, type IV collagen, and MCP-1. In rhTGF-β1-stimulated NHLFs, PXS64 (1–10 μM; 24.5 hours) significantly suppresses fibrotic markers such as fibronectin and collagen. Treatment with PXS64 (10 µM; 24 hours) improves fibroblast morphology and reduces levels of fibrotic markers including collagen, CTGF, TGF-β3, tenascin C, αSMA, and THBS1. In HF19 cells, PXS64 shows potent anti-fibrotic activity by inhibiting αSMA, fibronectin, and collagen.

Administered as an intraperitoneal injection at 10 μM once daily for seven consecutive days, PXS 64 improves renal fibrosis in male C57BL/6 mice [UUO model].