Design strategies for the identification of MMP-13 and Tace inhibitors
- PMID: 14579524
Design strategies for the identification of MMP-13 and Tace inhibitors
Abstract
Inhibitors of matrix metalloprotease (MMP)-13 and tumor necrosis factor-alpha converting enzyme (TACE) have been highly sought as potential therapeutic agents for the treatment of osteoarthritis and rheumatoid arthritis, respectively. This review focuses on the published literature on these inhibitors from 2001 to mid-2003. Significant advances have been reported in the design and synthesis of potent and selective inhibitors of MMP-13 using hydroxamic acid and non-hydroxamate zinc chelators on a variety of scaffolds. TACE inhibitors based on variations of known MMP inhibitors scaffolds and novel designs have been reported. Selectivity profiles for these inhibitors range from broad-spectrum to TACE-specific. Future clinical studies on these and other inhibitors will determine which MMP, or set of MMPs, must be inhibited for efficacy and long-term safety.
Similar articles
-
The design and synthesis of aryl hydroxamic acid inhibitors of MMPs and TACE.Curr Top Med Chem. 2004;4(12):1289-310. doi: 10.2174/1568026043387935. Curr Top Med Chem. 2004. PMID: 15320727 Review.
-
N-O-isopropyl sulfonamido-based hydroxamates: design, synthesis and biological evaluation of selective matrix metalloproteinase-13 inhibitors as potential therapeutic agents for osteoarthritis.J Med Chem. 2009 Aug 13;52(15):4757-73. doi: 10.1021/jm900261f. J Med Chem. 2009. PMID: 19606871
-
Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-alpha converting enzyme.Bioorg Med Chem Lett. 2005 Jun 15;15(12):2970-3. doi: 10.1016/j.bmcl.2005.04.039. Bioorg Med Chem Lett. 2005. PMID: 15908214
-
Synthesis and structure-activity relationship of alpha-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis.J Med Chem. 2003 Jun 5;46(12):2361-75. doi: 10.1021/jm0205548. J Med Chem. 2003. PMID: 12773041
-
The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.Curr Top Med Chem. 2004;4(12):1311-27. doi: 10.2174/1568026043387999. Curr Top Med Chem. 2004. PMID: 15320728 Review.
Cited by
-
Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model.Inflamm Res. 2013 Jan;62(1):17-25. doi: 10.1007/s00011-012-0546-3. Epub 2012 Aug 18. Inflamm Res. 2013. PMID: 22903188
-
Unlike for human monocytes after LPS activation, release of TNF-α by THP-1 cells is produced by a TACE catalytically different from constitutive TACE.PLoS One. 2012;7(3):e34184. doi: 10.1371/journal.pone.0034184. Epub 2012 Mar 30. PLoS One. 2012. PMID: 22479555 Free PMC article.
-
Anticytokine therapy for osteoarthritis: evidence to date.Drugs Aging. 2010 Feb 1;27(2):95-115. doi: 10.2165/11319950-000000000-00000. Drugs Aging. 2010. PMID: 20104937
-
Lubricin: a novel potential biotherapeutic approaches for the treatment of osteoarthritis.Mol Biol Rep. 2011 Jun;38(5):2879-85. doi: 10.1007/s11033-010-9949-9. Epub 2010 Jan 23. Mol Biol Rep. 2011. PMID: 20099082 Review.
-
Reactions of N-benzyloxycarbamate derivatives with stabilized carbon nucleophiles: a new synthetic approach to polyhydroxamic acids and other hydroxamate-containing mixed ligand systems.J Org Chem. 2009 Jan 16;74(2):782-8. doi: 10.1021/jo802410u. J Org Chem. 2009. PMID: 19063593 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Miscellaneous