PXS-5153A monohydrochloride is a potent, selective, orally active and fast-acting lysyl oxidase like 2/3 enzymatic (LOXL2/LOXL3) inhibitor, with an IC 50 of <40 nM for LOXL2 across all mammalian species and an IC 50 of 63 nM for human LOXL3. PXS-5153A monohydrochloride dose-dependently reduced LOXL2-mediated collagen oxidation and collagen crosslinking in vitro which may represent an innovative therapeutic approach for the treatment of fibrosis

PXS-5153A shows an IC 50 of <40 nM for LOXL2 across all mammalian species tested. PXS-5153A also inhibits human LOXL3 with an IC 50 value of 63 nM. PXS-5153A is >40-fold selective for LOXL2 over both LOX and LOXL1 and >700-fold selective over other related amine oxidases. PXS-5153A is a fast-acting inhibitor, with enzymatic activity almost entirely blocked within 15 minutes [1].

As expected, rhLOXL2 induces collagen oxidation in a dose-dependent manner while PXS-5153A impedes collagen oxidation in a dose-dependent manner. Therapeutic treatment of PXS-5153A substantially reduces immature crosslink formation compared with the CCl 4 treated animals. Mature crosslink formation is also reduced by PXS-5153A treatment. All groups with therapeutic treatment of PXS-5153A show a significant reduction in DHLNL formation compared to the CCl 4 treated animals. Treatment with PXS-5153A causes a significantly reduction in HYP compared to the CCl 4 group. In addition, the amount of fibrillar collagen is markedly augmented by disease as seen by the 2.2-fold increase in percentage coverage area by Picrosirius red staining, which is reduced by PXS-5153A [1].