ArticleFEBS letters2018
Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14.
Article in FEBS letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Modifying inhibitor specificity for homologous enzymes by machine learning.The FEBS journal · 2026Article
- Engineering Single-Chain Antibody Fragment (scFv) Variants Targeting A Disintegrin and Metalloproteinase-17 (ADAM-17).Biomolecules · 2025Article
- Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.Biomolecules · 2025Article
- Matrix Metalloproteinases and Their Inhibitors in the Pathogenesis of Epithelial Differentiation, Vascular Disease, Endometriosis, and Ocular Fibrotic Pterygium.International journal of molecular sciences · 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
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Designed Loop Extension Followed by Combinatorial Screening Confers High Specificity to a Broad Matrix MetalloproteinaseInhibitor.Journal of molecular biology · 2023Article
- The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma.Molecules (Basel, Switzerland) · 2023Review
- Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.bioRxiv : the preprint server for biology · 2023Article
- Dietary artemisinin boosts intestinal immunity and healthy in fat greenling (Frontiers in immunology · 2023Article
- Structure and computation-guided yeast surface display for the evolution of TIMP-based matrix metalloproteinase inhibitors.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
MMP-14 and MMP-9 are two well-established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a nonspecific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity toward MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.
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What OpenQuestion holds
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.