ArticleThe Journal of biological chemistry2017
Development of High Affinity and High Specificity Inhibitors of Matrix Metalloproteinase 14 through Computational Design and Directed Evolution.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 81 citations in OpenAlex.
- A protein-small molecule conjugate as a bispecific inhibitor of proteases implicated in cancer metastasis.Scientific reports · 2026Article
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis.Journal of translational medicine · 2026Article
- Modifying inhibitor specificity for homologous enzymes by machine learning.The FEBS journal · 2026Article
- Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.Biomolecules · 2025Article
- Matrix Metalloproteinases: Pathophysiologic Implications and Potential Therapeutic Targets in Cardiovascular Disease.Biomolecules · 2025Review
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Mirror-Image Random Nonstandard Peptides Integrated Discovery (MI-RaPID) Technology Yields Highly Stable and Selective Macrocyclic Peptide Inhibitors for Matrix Metallopeptidase 7.Angewandte Chemie (International ed. in English) · 2025Article
- Engineered TIMP2 with narrow MMP-9 specificity is an effective inhibitor of invasion and proliferation of triple-negative breast cancer cells.The Journal of biological chemistry · 2024Article
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.Biomolecules · 2024Article
- Deep neural networks for predicting the affinity landscape of protein-protein interactions.iScience · 2024Article
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.bioRxiv : the preprint server for biology · 2024Article
- Engineering metalloproteinase inhibitors: tissue inhibitors of metalloproteinases or antibodies, that is the question.Current opinion in biotechnology · 2024Review
- Engineering Selective TIMPs Using a Counter-Selective Screening Strategy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Engineering minimal tissue inhibitors of metalloproteinase targeting MMPs via gene shuffling and yeast surface display.Protein science : a publication of the Protein Society · 2023Article
- Computational design of matrix metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.The Biochemical journal · 2023Article
- Designed Loop Extension Followed by Combinatorial Screening Confers High Specificity to a Broad Matrix MetalloproteinaseInhibitor.Journal of molecular biology · 2023Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as 3 decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment. In this study, we integrated a computational method and a yeast surface display technique to obtain highly specific inhibitors of MMP-14 by modifying the natural non-specific broad MMP inhibitor protein N-TIMP2 to interact optimally with MMP-14. We identified an N-TIMP2 mutant, with five mutations in its interface, that has an MMP-14 inhibition constant (
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.