1vsn
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Based on our previous study with trifluoroethylamine as a P2-P3 amide | + | Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Pycnodysostosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601105 601105]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1VSN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NFT:'>NFT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 1VSN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NFT:'>NFT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 2FDZ. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VSN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: structure-guided drug design]] | [[Category: structure-guided drug design]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:19 2008'' |
Revision as of 13:38, 21 February 2008
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Crystal structure of a potent small molecule inhibitor bound to cathepsin K
Contents |
Overview
Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
1VSN is a Single protein structure of sequence from Homo sapiens with as ligand. This structure supersedes the now removed PDB entry 2FDZ. Active as Cathepsin K, with EC number 3.4.22.38 Full crystallographic information is available from OCA.
Reference
Identification of a potent and selective non-basic cathepsin K inhibitor., Li CS, Deschenes D, Desmarais S, Falgueyret JP, Gauthier JY, Kimmel DB, Leger S, Masse F, McGrath ME, McKay DJ, Percival MD, Riendeau D, Rodan SB, Therien M, Truong VL, Wesolowski G, Zamboni R, Black WC, Bioorg Med Chem Lett. 2006 Apr 1;16(7):1985-9. Epub 2006 Jan 18. PMID:16413777
Page seeded by OCA on Thu Feb 21 15:38:19 2008
