2. Academic Validation
  3. The Multitarget Compound ZLY032 Achieves Treatment of Chronic Wounds

The Multitarget Compound ZLY032 Achieves Treatment of Chronic Wounds

  • Adv Sci (Weinh). 2025 Jul 17:e03098. doi: 10.1002/advs.202503098.
Manyu Gong 1 2,  Zhiyuan Du 1,  Tiantian Gong 1,  Yu Wang 1,  Chenchen Yin 1,  Bosi Sun 1,  Zijia Liu 1,  Lianru Chen 3,  Zibin Liao 3,  Wenxin Wang 3,  Tianjiao Zhao 1,  Yifei Wang 1,  Ying Dong 4,  Kexin Wang 1,  Mengru Ma 1,  Weijun Li 1,  Jiacheng Li 1,  Haodong Li 1,  Congcong Lin 5,  Ying Zhang 1,  Yu Liu 1,  Xin Liu 1,  Tao Ban 1,  Hongxia Bao 6,  Ying Zhang 1,  Yang Zhang 1,  Zheng Li 3,  Lei Jiao 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and Natural Medicine Chemistry, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, P. R. China.
  • 2 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, China.
  • 3 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
  • 4 The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, China.
  • 5 Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, China.
  • 6 Genomics Research Center, Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, China.
PMID: 40673882 DOI: 10.1002/advs.202503098
Abstract

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.

Keywords

ZLY032; antibacterial; anti‐inflammatory; argininosuccinate lyase; chronic wounds.

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