This invention discloses a mitochondrial uncoupling agent
prodrug with endothelial
cell targeting, its preparation method, and its application, relating to the field of
biomedical technology. The
prodrug is covalently coupled to a vascular
cell adhesion molecule-1 targeting polypeptide (
amino acid sequence FAKELMEEFEKW), a
reactive oxygen species-sensitive thioacetate
linker, and the mitochondrial uncoupling agent OPC-163493. This invention utilizes the active enrichment effect of the targeting polypeptide on inflamed pulmonary vascular endothelial cells, overcoming the off-target defects of non-specific distribution in existing
small molecule drugs; simultaneously, it utilizes the specific cleavage characteristics of the thioacetate
linker in a microenvironment rich in
reactive oxygen species to achieve precise in-situ
drug release. This
prodrug can effectively reduce mitochondrial
reactive oxygen species generation, inhibit
endothelial cell apoptosis, significantly reduce pulmonary
vascular permeability, and alleviate
pulmonary edema, possessing significant clinical application value in the preparation of drugs for treating acute
lung injury or
acute respiratory distress syndrome.