doi: 10.1021/ja054558o.
Potent, selective pyrone-based inhibitors of stromelysin-1
Affiliations
- PMID: 16218585
- DOI: 10.1021/ja054558o
Item in Clipboard
Potent, selective pyrone-based inhibitors of stromelysin-1
J Am Chem Soc.
.
Abstract
In an effort to develop alternatives to hydroxamate-based matrix metalloproteinase inhibitors (MPIs), we have utilized the drug discovery program LUDI enhanced with the structural coordinates of a bioinorganic model complex. This method has yielded the first pyrone-based MPIs. The inhibitors demonstrate nanomolar potency against MMP-3 and are selective for MMP-3 over MMP-2 and MMP-1. We postulate that the potency and unusual selectivity profile of these MPI is attributable to the pyrone chelating group.
Similar articles
-
New beginnings for matrix metalloproteinase inhibitors: identification of high-affinity zinc-binding groups.J Am Chem Soc. 2004 Jul 14;126(27):8388-9. doi: 10.1021/ja0485513. J Am Chem Soc. 2004. PMID: 15237990
-
A novel series of highly selective inhibitors of MMP-3.Bioorg Med Chem Lett. 2007 Dec 15;17(24):6750-3. doi: 10.1016/j.bmcl.2007.10.042. Epub 2007 Oct 17. Bioorg Med Chem Lett. 2007. PMID: 18029177
-
Inhibition of stromelysin-1 (MMP-3) by P1'-biphenylylethyl carboxyalkyl dipeptides.J Med Chem. 1997 Mar 14;40(6):1026-40. doi: 10.1021/jm960465t. J Med Chem. 1997. PMID: 9083493
-
Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs.Biochimie. 2005 Mar-Apr;87(3-4):393-402. doi: 10.1016/j.biochi.2004.09.025. Biochimie. 2005. PMID: 15781327 Review.
-
Matrix metalloproteinase 11 (MMP-11; stromelysin-3) and synthetic inhibitors.Med Res Rev. 2007 Jul;27(4):528-52. doi: 10.1002/med.20066. Med Res Rev. 2007. PMID: 16710861 Review.
Cited by
-
Investigating chelating sulfonamides and their use in metalloproteinase inhibitors.Dalton Trans. 2012 Jun 7;41(21):6507-15. doi: 10.1039/c2dt12373h. Epub 2012 Mar 12. Dalton Trans. 2012. PMID: 22411188 Free PMC article.
-
Efficient synthesis of 5-amido-3-hydroxy-4-pyrones as inhibitors of matrix metalloproteinases.Org Lett. 2007 Jun 21;9(13):2517-20. doi: 10.1021/ol0707665. Epub 2007 May 24. Org Lett. 2007. PMID: 17521196 Free PMC article.
-
Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders.Prog Mol Biol Transl Sci. 2017;148:355-420. doi: 10.1016/bs.pmbts.2017.04.003. Epub 2017 May 10. Prog Mol Biol Transl Sci. 2017. PMID: 28662828 Free PMC article. Review.
-
Including receptor flexibility and induced fit effects into the design of MMP-2 inhibitors.J Mol Recognit. 2010 Mar-Apr;23(2):173-82. doi: 10.1002/jmr.989. J Mol Recognit. 2010. PMID: 19882751 Free PMC article.
-
Application of metal coordination chemistry to explore and manipulate cell biology.Chem Rev. 2009 Oct;109(10):4921-60. doi: 10.1021/cr900134a. Chem Rev. 2009. PMID: 19715312 Free PMC article. Review. No abstract available.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
