2. Academic Validation
  3. Docking and database screening identify manidipine as a potential modulator of matrix metalloproteinase-7 in chronic kidney disease

Docking and database screening identify manidipine as a potential modulator of matrix metalloproteinase-7 in chronic kidney disease

  • Biomed Pharmacother. 2025 Dec:193:118748. doi: 10.1016/j.biopha.2025.118748.
Chia-Te Liao 1,  Yen-Chung Lin 2,  Hung-Jin Huang 3,  Wen-Chih Liu 4,  Wei-Chih Kan 5,  Hui-Wen Chiu 6
Affiliations

Affiliations

  • 1 Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
  • 2 Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
  • 3 Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 4 Section of Nephrology, Department of Medicine, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan; Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: [email protected].
  • 5 Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan. Electronic address: [email protected].
  • 6 TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 41232355 DOI: 10.1016/j.biopha.2025.118748
Abstract

Matrix Metalloproteinases (MMPs) are a critical family of proteolytic Enzymes responsible for extracellular matrix (ECM) remodeling and degradation. Among them, MMP7 has emerged as a key regulator in the pathogenesis of kidney diseases, exerting a more pronounced influence than Other MMPs. In this study, we aimed to identify a potential bioactive drug targeting MMP7 and investigate its molecular mechanisms in chronic kidney disease (CKD) using both in vitro and in vivo models. A virtual drug screening was employed to discover candidate compounds with high affinity to the MMP7 target protein using the DrugBank database. The biological effects of the identified drug were subsequently validated through in vitro experiments in kidney cells and in vivo studies using a CKD mouse model. Manidipine reduced MMP7 enzymatic activity by a fluorogenic peptide substrate. Manidipine functionally enhanced Autophagy while suppressing NLRP3/NLRP6 inflammasome activation in kidney cells in vitro and in vivo. Additionally, manidipine significantly downregulated the expression of fibrosis-related proteins, leading to a reduction in renal fibrosis. In experimental CKD models, manidipine treatment improved renal function and mitigated structural kidney damage. Manidipine attenuated the progression of CKD by regulating MMP7 activity, Autophagy, inflammasomes and fibrosis in kidney tissues. These findings reveal a novel renoprotective mechanism of manidipine, suggesting its potential as a therapeutic agent for attenuating CKD progression.

Keywords

Chronic kidney disease; Docking-based virtual screening platform; Manidipine; Matrix metalloproteinase-7.

Figures
Products
Inhibitors & Agonists
Other Products