ArticlePloS one2015
Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01803282 (A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 120 papers.
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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.
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.
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors
Who cites it
120 citing papers in PubMed, 191 citations in OpenAlex.
- 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
- A Phase 2, Randomized, Placebo-Controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients With Moderately to Severely Active Crohn's Disease.Journal of Crohn's & colitis · 2018Trial
- 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
- Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.Alimentary pharmacology & therapeutics · 2016Trial
- Matrix Metalloproteinase-9 (MMP-9) in Psoriasis: Integrating Extracellular Matrix Remodeling, Neutrophil-Endothelial Crosstalk and Biomarker Evidence.Medical sciences (Basel, Switzerland) · 2026Review
- Timing-dependent protective and therapeutic effects of ethyl pyruvate in trinitrobenzene sulfonic acid-induced experimental colitis.Experimental physiology · 2026Article
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- Loss of proton-sensing TDAG8 increases tumor progression in mouse models of colon cancer.Molecular oncology · 2026Article
- Review
- Predicting Clinical Response to Granulocyte/Monocyte Adsorption Apheresis in Treatment-Resistant Ulcerative Colitis.Gastro hep advances · 2026Article
- Manuka honey and its component, methyl syringate, shift neutrophil release profiles from pro-inflammatory while preserving pro-regenerative growth factor releaseFrontiers in immunology · 2026Article
- Screening Co-Diagnostic Genes for Lung Adenocarcinoma and Myocardial Infarction and Analysis of the Molecular Functions and Drug Value of the GenesEndocrine, metabolic & immune disorders drug targets · 2026Article
- Epigenetic drivers of metalloproteinases and metastasis.Trends in cell biology · 2025Review
- The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer.Journal of leukocyte biology · 2025Review
- Loss of proton-sensing GPR4 reduces tumor progression in mouse models of colon cancer.Molecular oncology · 2025Article
- Matrix Dynamics and Microbiome Crosstalk: Matrix Metalloproteinases as Key Players in Disease and Therapy.International journal of molecular sciences · 2025Review
- A tailored 4GRSC advances · 2025Article
- Analysis of the molecular mechanisms of ulcerative colitis and atherosclerosis by microarray data.Scientific reports · 2025Article
- The edible ethanol extract ofNutrition research and practice · 2025Article
- Harnessing synergistic effects of MMP-2 Inhibition and bFGF to simultaneously preserve and vascularize cardiac extracellular matrix after myocardial infarction.Acta biomaterialia · 2025Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of matrix metalloproteinase 9 (MMP9) is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs), including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors) in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients.
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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.