ArticleThe Journal of biological chemistry2017
Biochemical characterization and structure determination of a potent, selective antibody inhibitor of human MMP9.
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 55 papers.
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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.
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Who cites it
55 citing papers in PubMed, 120 citations in OpenAlex.
- Randomized, open-label, phase 2 study of andecaliximab plus nivolumab versus nivolumab alone in advanced gastric cancer identifies biomarkers associated with survival.Journal for immunotherapy of cancer · 2021Trial
- Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Andecaliximab [Anti-matrix Metalloproteinase-9] Induction Therapy for Ulcerative Colitis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2/3 Study in Patients With Moderate to Severe Disease.Journal of Crohn's & colitis · 2018Trial
- Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.Science translational medicine · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Pharmacophore-driven antibody discovery on the yeast surface.bioRxiv : the preprint server for biology · 2025Article
- Matrix Metalloproteinase-9: A Key Diagnostic Biomarker in Cancer Progression.Current drug targets · 2025Review
- Determining key residues of engineered scFv antibody variants with improved MMP-9 binding using deep sequencing and machine learning.Computational and structural biotechnology journal · 2024Article
- 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
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.bioRxiv : the preprint server for biology · 2024Article
- A general approach for selection of epitope-directed binders to proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification, Antioxidant Capacity, and Matrix Metallopeptidase 9 (MMP-9) In Silico Inhibition of Haloarchaeal Carotenoids fromMicroorganisms · 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
- Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.bioRxiv : the preprint server for biology · 2023Article
- Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane.Molecules (Basel, Switzerland) · 2023Article
- Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody.Antibodies (Basel, Switzerland) · 2023Article
- Evaluation of the matrix metalloproteinase 9 (MMP9) inhibitor Andecaliximab as an Anti-invasive therapeutic in Head and neck squamous cell carcinoma.Oral oncology · 2022Article
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinase 9 (MMP9) is a member of a large family of proteases that are secreted as inactive zymogens. It is a key regulator of the extracellular matrix, involved in the degradation of various extracellular matrix proteins. MMP9 plays a pathological role in a variety of inflammatory and oncology disorders and has long been considered an attractive therapeutic target. GS-5745, a potent, highly selective humanized monoclonal antibody inhibitor of MMP9, has shown promise in treating ulcerative colitis and gastric cancer. Here we describe the crystal structure of GS-5745·MMP9 complex and biochemical studies to elucidate the mechanism of inhibition of MMP9 by GS-5745. GS-5745 binds MMP9 distal to the active site, near the junction between the prodomain and catalytic domain, and inhibits MMP9 by two mechanisms. Binding to pro-MMP9 prevents MMP9 activation, whereas binding to active MMP9 allosterically inhibits activity.
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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.