PXS-5153A

PXS-5153A is a potent, selective, orally active and fast-acting lysyl oxidase like 2/3 enzymatic (LOXL2/LOXL3) inhibitor, with an IC₅₀ of <40 nM for LOXL2 across all mammalian species and an IC₅₀ of 63 nM for human LOXL3. PXS-5153A could reduce crosslinks and ameliorates fibrosis. IC50 & Target: IC50: <40 nM (LOXL2 across all mammalian species), 63 nM (human LOXL3)^[1]. In Vitro: PXS-5153A exhibits an IC₅₀ of <40 nM for LOXL2 across all mammalian species tested. PXS-5153A also inhibits human LOXL3 with an IC₅₀ 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]. In Vivo: As expected, rhLOXL2 dose-dependently induce oxidation of collagen with PXS-5153A dose-dependently impeding collagen oxidation. Therapeutic treatment of PXS-5153A substantially reduces immature crosslink formation compared with the CCl₄ 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 CCl₄ treated animals. Treatment with PXS-5153A causes a significantly reduction in HYP compared to the CCl₄ 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].