ArticleThe Journal of biological chemistry2024
Engineered TIMP2 with narrow MMP-9 specificity is an effective inhibitor of invasion and proliferation of triple-negative breast cancer cells.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Molecular insights into triazole-based compounds for triple-negative breast cancer treatment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Autophagy Orchestrates Anti-Tumor Immunity to Enhance Chemosensitivity via the FBXW2/C/EBPβ/TIMP-2 Axis in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A protein-small molecule conjugate as a bispecific inhibitor of proteases implicated in cancer metastasis.Scientific reports · 2026Article
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- Review
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- Advances in Extracellular Matrix Metalloproteinases: Implications for Renal Cell Carcinoma Pathophysiology, Diagnostics, and Therapeutics.Medicines (Basel, Switzerland) · 2026Review
- Modifying inhibitor specificity for homologous enzymes by machine learning.The FEBS journal · 2026Article
- MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.Protein & cell · 2026Article
- Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.Biomolecules · 2025Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade extracellular matrix proteins, functioning in various physiological processes such as tissue remodeling, embryogenesis, and morphogenesis. Dysregulation of these enzymes is linked to multiple diseases. Specific inhibition of particular MMPs is crucial for anti-MMP drug development as some MMPs have shown antidisease properties. In this study, we aimed to design a highly specific inhibitor of MMP-9, that plays a crucial role in cell invasion and metastasis, using tissue inhibitor of metalloproteinases 2 (TIMP2s), an endogenous broad-family MMP inhibitor, as a prototype. In our earlier work, we were able to narrow down the specificity of the N-terminal domain of TIMP2 (N-TIMP2) toward MMP-9, yet at the expense of lowering its affinity to MMP-9. In this study, a library of N-TIMP2 mutants based on previous design with randomized additional positions was sorted for binding to MMP-9 using yeast surface display. Two selected N-TIMP2 mutants were expressed, purified, and their inhibitory activity against a panel of MMPs was measured. The best engineered N-TIMP2 mutant (REY) exhibited a 2-fold higher affinity to MMP-9 than that of the WT N-TIMP2, and 6- to 1.1 x 10
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