ArticlePloS one2012
PEGylation extends circulation half-life while preserving in vitro and in vivo activity of tissue inhibitor of metalloproteinases-1 (TIMP-1).
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics.Journal of the American Chemical Society · 2026Article
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- CRISPR-AuNP: physicochemical optimization of a gold nanoparticle platform for cost-effective and modular non-viral gene editing in HSPCs.Gene therapy · 2026Article
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Histidine Tag-Specific PEGylation Improves the Circulating Half-Life of TIMP2.ACS applied bio materials · 2025Article
- Phage-derived proteins: Advancing food safety through biocontrol and detection of foodborne pathogens.Comprehensive reviews in food science and food safety · 2025Review
- Polyethylene Glycolylation of the Purified Basic Protein (Protamine) of Squid (International journal of molecular sciences · 2025Article
- Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.Current cancer drug targets · 2025Review
- Innovative Formulation Platform: Paving the Way for Superior Protein Therapeutics with Enhanced Efficacy and Broadened Applications.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.Biomolecules · 2024Article
- Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.Dermatology and therapy · 2024Review
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.bioRxiv : the preprint server for biology · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach.Journal of nanobiotechnology · 2023Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Bioorthogonal PEGylation Prolongs the Elimination Half-Life of N-TIMP2 While Retaining MMP Inhibition.Bioconjugate chemistry · 2022Article
- Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model.International journal of molecular sciences · 2021Article
- Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics.Cells · 2020Review
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Excess proteolytic activity of matrix metalloproteinases (MMPs) contributes to the development of arthritis, cardiovascular diseases and cancer progression, implicating these enzymes as therapeutic targets. While many small molecule inhibitors of MMPs have been developed, clinical uses have been limited, in part by toxicity and off-target effects. Development of the endogenous tissue inhibitors of metalloproteinases (TIMPs) as recombinant biopharmaceuticals represents an alternative therapeutic approach; however, the short plasma half-life of recombinant TIMPs has restricted their potential in this arena. To overcome this limitation, we have modified recombinant human TIMP-1 (rhTIMP-1) by PEGylation on lysine residues. We analyzed a mixture of mono- and di-PEGylated rhTIMP-1 species modified by attachment of 20 kDa mPEG chains (PEG(20K)-TIMP-1), as confirmed by SELDI-TOF mass spectrometry. This preparation retained complete inhibitory activity toward the MMP-3 catalytic domain and partial inhibitory activity toward full length MMP-9. Pharmacokinetic evaluation showed that PEGylation extended the plasma half-life of rhTIMP-1 in mice from 1.1 h to 28 h. In biological assays, PEG(20K)-TIMP-1 inhibited both MMP-dependent cancer cell invasion and tumor cell associated gelatinase activity. Overall these results suggest that PEGylated TIMP-1 exhibits improved potential for development as an anti-cancer recombinant protein therapeutic, and additionally may offer potential for clinical applications in the treatment of other diseases.
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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.