Design and synthetic considerations of matrix metalloproteinase inhibitors
- PMID: 10415720
- DOI: 10.1111/j.1749-6632.1999.tb07674.x
Design and synthetic considerations of matrix metalloproteinase inhibitors
Abstract
Experimental evidence confirms that the matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions that involve connective tissue destruction including osteoarthritis and rheumatoid arthritis, tumor metastasis and angiogenesis, corneal ulceration, multiple sclerosis, periodontal disease, and atherosclerosis. Modulation of MMP regulation is possible at several biochemical sites, but direct inhibition of enzyme action provides a particularly attractive target for therapeutic intervention. Hypotheses concerning inhibition of specific MMP(s) with respect to disease target and/or side-effect profile have emerged. Examples are presented of recent advances in medicinal chemistry approaches to the design of matrix metalloproteinase inhibitors (MMPIs), approaches that address structural requirements and that influence potency, selectivity, and bioavailability. Two important approaches to the design, synthesis, and biological evaluation of MMPIs are highlighted: (1) the invention of alternatives to hydroxamic acid zinc chelators and (2) the construction of nonpeptide scaffolds. One current example in each of these two approaches from our own work is described.
Similar articles
-
Design strategies for the identification of MMP-13 and Tace inhibitors.Curr Opin Drug Discov Devel. 2003 Sep;6(5):742-59. Curr Opin Drug Discov Devel. 2003. PMID: 14579524 Review.
-
Metalloproteinase inhibitors as therapeutics.Clin Exp Rheumatol. 1993 Mar-Apr;11 Suppl 8:S91-4. Clin Exp Rheumatol. 1993. PMID: 8391953 Review.
-
Matrix metalloproteinase inhibitors: applications in oncology.Invest New Drugs. 1999;17(4):387-99. doi: 10.1023/a:1006386406584. Invest New Drugs. 1999. PMID: 10759405 Review.
-
Matrix metalloproteinase inhibitors: present achievements and future prospects.Invest New Drugs. 1997;15(3):175-85. doi: 10.1023/a:1005855905442. Invest New Drugs. 1997. PMID: 9387040 Review.
-
The inhibition of metalloproteinases as a therapeutic target in rheumatoid arthritis and osteoarthritis.Curr Opin Pharmacol. 2001 Jun;1(3):314-20. doi: 10.1016/s1471-4892(01)00055-8. Curr Opin Pharmacol. 2001. PMID: 11712757 Review.
Cited by
-
Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.Int J Nanomedicine. 2012;7:1163-73. doi: 10.2147/IJN.S27860. Epub 2012 Mar 1. Int J Nanomedicine. 2012. PMID: 22419865 Free PMC article.
-
Targeting Angiogenesis in Rheumatoid Arthritis.Curr Rheumatol Rev. 2008 Nov 1;4(4):298-303. doi: 10.2174/157339708786263942. Curr Rheumatol Rev. 2008. PMID: 20706557 Free PMC article.
-
New insights in synovial angiogenesis.Joint Bone Spine. 2010 Jan;77(1):13-9. doi: 10.1016/j.jbspin.2009.05.011. Epub 2009 Dec 21. Joint Bone Spine. 2010. PMID: 20022538 Free PMC article. Review.
-
Angiogenesis in rheumatoid arthritis.Autoimmunity. 2009 Nov;42(7):563-73. doi: 10.1080/08916930903143083. Autoimmunity. 2009. PMID: 19863375 Free PMC article. Review.
-
Angiogenesis and its targeting in rheumatoid arthritis.Vascul Pharmacol. 2009 Jul;51(1):1-7. doi: 10.1016/j.vph.2009.02.002. Epub 2009 Feb 13. Vascul Pharmacol. 2009. PMID: 19217946 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources