Inhibition of LOXL2 and Other Lysyl Oxidase (Like) Enzymes: Intervention at the Core of Fibrotic Pathology
The hallmark of fibrosis is the accumulation of excessive collagen in tissue as a result of an imbalance between collagen formation and degradation. A key step in collagen formation is its stabilization – and with this, slowing of its degradation – by cross-links. This cross-linking is mediated by lysyl oxidases, a group of five related enzymes consisting of lysyloxidase (LOX) and lysyl oxidase like 1–4 (LOXL1–4), of which LOXL2 is thought to be of particular relevance in most conditions of pathological fibrosis. Recently, the first inhibitors of LOXL2 enzyme activity and dual inhibitors of LOXL2 and LOXL3 have been advanced into clinical studies. The data underlying their promise as novel anti-fibrotic therapeutics is summarised, together with an outlook on the potential of inhibition of other members of this family of enzymes.