产品描述:
PXS-5505 is a pan inhibitor of lysyl oxidase (LOX) and LOX-like oxidases (LOXL; IC50s = 0.493, 0.159, 0.57, 0.18, and 0.19 µM for fibroblast LOX and recombinant human LOXL1-4, respectively).{69837} It is selective for LOX and LOXL1-4 over other recombinant human oxidases, including diamine oxidase (DAO), vascular adhesion protein-1 (VAP-1), monoamine oxidase A (MAO-A), and MAO-B (IC50s = >30 µM for all). PXS-5505 (15 mg/kg) reduces bleomycin-induced increases in dermal thickness and the levels of α-smooth muscle actin in a mouse model of systemic sclerosis.{69838} It reduces fibrosis in rodent models of bleomycin-induced pulmonary fibrosis, cardiac ischemia-reperfusion injury, renal unilateral ureteral obstruction, and carbon tetrachloride-induced liver fibrosis. It also reduces collagen crosslinking in KPC cancer-associated fibroblast (CAF) 3D organotypic matrices.{69837} PXS-5505 (20 mg/kg) increases survival to a greater extent than gemcitabine alone when administered in combination with the anticancer nucleoside derivative gemcitabine (Item Nos. 11690 | 9003096), reduces gemcitabine-induced increases in collagen levels and stiffness, and reduces liver metastatic burden in autochthonous KPC pancreatic ductal adenocarcinoma mouse models.