Target intelligence / Profile preview

Lysyl oxidase-like 2 (LOXL2) (LOXL2)

Target
LOXL2
Molecular classification
Enzyme, Amine oxidase, Copper-dependent enzyme, Lysyl oxidase family
01

Overview

Lysyl oxidase-like 2 (LOXL2) is a copper-dependent amine oxidase that plays a critical role in the remodeling of the extracellular matrix (ECM) by catalyzing the cross-linking of collagen and elastin (UniProt Q9Y4K0). Beyond its structural role, LOXL2 is involved in intracellular signaling pathways, notably the stabilization of the transcription factor Snail, which promotes epithelial-mesenchymal transition (EMT) and tumor metastasis (PubMed: 23226001). In pathological states, over-expression of LOXL2 is strongly associated with various fibrotic diseases, including idiopathic pulmonary fibrosis and liver cirrhosis, as well as the progression of several cancers (PubMed: 28103437). Therapeutic strategies targeting LOXL2 include monoclonal antibodies like simtuzumab and small molecule inhibitors like PXS-5382, designed to reduce ECM stiffness and inhibit metastatic potential (ClinicalTrials.gov: NCT01769196). While clinical trials for some LOXL2 inhibitors have faced challenges regarding efficacy, the target remains a high-interest area for treating chronic fibroproliferative disorders and solid tumors.

Other names
Lysyl oxidase homolog 2LOR2WS9-14Lysyl oxidase-related protein 2
02

Mechanism of action

Inhibition of the amine oxidase activity to prevent collagen cross-linking and suppress epithelial-mesenchymal transition (PubMed: 23226001).

03

Biological functions

Extracellular matrix remodelingCollagen cross-linkingEpithelial-mesenchymal transitionSnail stabilizationCell migration
04

Disease associations

FibrosisCancerCardiovascular diseaseIdiopathic pulmonary fibrosisNonalcoholic steatohepatitis (NASH)
05

Safety considerations

Selectivity over LOX (PubMed: 23226001)Vascular integrity risksSystemic effects of long-term inhibition
06

Interacting drugs

Simtuzumab

3 more in the full profile.

07

Biomarkers

Serum LOXL2 levels (PubMed: 28103437)Pro-C3 (ClinicalTrials.gov: NCT01769196)

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