The Multitarget Compound ZLY032 Achieves Treatment of Chronic Wounds.

The approach to dealing with chronic wounds is still challenging in clinic. Multitarget drugs have the advantages of superior therapeutic effect and minimal adverse reactions. The aim of the present study is to develop a multitarget treatment strategy for skin wound healing. It is showed here that topical application of ZLY032, a dual free fatty acid receptor 1 (FFA1)/peroxisome proliferator-activated receptor (PPARδ) agonist, accelerates the healing of full-thickness skin wounds in both normal mice and rabbits, even in the diabetic mice and methicillin-resistant Staphylococcus aureus (MRSA) infected mice. At the eukaryotic cell level, ZLY032 shows the ability to accelerate angiogenesis and inhibit inflammation via targeting PPARδ and FFA1. At the prokaryotic cell level, ZLY032 exhibits antibacterial activity against Staphylococcus aureus and MRSA via targeting argininosuccinate lyase (ASAL, argH). At the application level, ZLY032-loaded microneedles demonstrate a therapeutic effect on wound healing in rabbits with an improved dosing frequency. In this work, ZLY032 application is verified as a potential multitarget strategy for wound healing with good safety and efficacy. Furthermore, the discovery of the antimicrobial target of ZLY032 provides a theoretical basis for the development of novel antibiotics against drug-resistant strains.