A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms.

PAT-1251 at the low dose of 30 mg/kg demonstrated a clear trend to reduced portal hypertension, with average portal venous pressure lowered by 1.7 mm Hg compared with the placebo group, although this did not reach statistical significance.

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Quantitative morphometry revealed a highly significant 6.7-fold reduction in Ki-67(+) ductal cells, paralleled by a 3.8-fold increase in Ki-67(+) hepatocytes in the high dose PAT-1251–treated mice (Figure 3 D) and robust suppression of transcripts of ductular reaction/HPC activation markers CK19, Trop2, and EpCAM (Figure 3 E).

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