ArticleArthritis research & therapy2007
Methionine aminopeptidase-2 blockade reduces chronic collagen-induced arthritis: potential role for angiogenesis inhibition.
Article in Arthritis research & therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Therapeutic Targets and Signaling Mechanisms in 2D and 3D In Vitro Models of Osteoarthritis.Clinical anatomy (New York, N.Y.) · 2026Review
- Common therapeutic target for both cancer and obesity.World journal of biological chemistry · 2017Article
- Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Review
- Fumagillin prodrug nanotherapy suppresses macrophage inflammatory response via endothelial nitric oxide.ACS nano · 2014Article
- Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis.Therapeutic advances in musculoskeletal disease · 2014Review
- Orally active fumagillin analogues: transformations of a reactive warhead in the gastric environment.ACS medicinal chemistry letters · 2013Article
- Computational validation of 3-ammonio-3-(4-oxido- 1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) as a potent anti-tubercular drug against mt-MetAP.Bioinformation · 2012Article
- Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade.Arthritis research & therapy · 2011Article
- The vasculature in rheumatoid arthritis: cause or consequence?International journal of experimental pathology · 2009Review
- Involution of collagen-induced arthritis with an angiogenesis inhibitor, PPI-2458.The Journal of pharmacology and experimental therapeutics · 2009Article
- Immunomodulatory activity of a methionine aminopeptidase-2 inhibitor on B cell differentiation.Clinical and experimental immunology · 2009Article
- Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.Arthritis research & therapy · 2008Article
- Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation, and as such provides a valuable target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased synovial vascularity, and hence is a potential therapeutic target for angiogenesis inhibitors. We examined the use of PPI-2458, a selective non-reversible inhibitor of MetAP-2, in disease models of RA, namely acute and chronic collagen-induced arthritis (CIA) in mice. Whilst acute CIA is a monophasic disease, CIA induced with murine collagen type II manifests as a chronic relapsing arthritis and mimics more closely the disease course of RA. Our study showed PPI-2458 was able to reduce clinical signs of arthritis in both acute and chronic CIA models. This reduction in arthritis was paralleled by decreased joint inflammation and destruction. Detailed mechanism of action studies demonstrated that PPI-2458 inhibited human endothelial cell proliferation and angiogenesis in vitro, without affecting production of inflammatory cytokines. Furthermore, we also investigated release of inflammatory cytokines and chemokines from human RA synovial cell cultures, and observed no effect of PPI-2458 on spontaneous expression of cytokines and chemokines, or indeed on the angiogenic molecule vascular endothelial growth factor (VEGF). These results highlight MetAP-2 as a good candidate for therapeutic intervention in RA.
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