1vsn
From Proteopedia
(New page: 200px<br /> <applet load="1vsn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vsn, resolution 2.000Å" /> '''Crystal structure ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1vsn. | + | [[Image:1vsn.jpg|left|200px]]<br /><applet load="1vsn" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1vsn" size=" | + | |
caption="1vsn, resolution 2.000Å" /> | caption="1vsn, resolution 2.000Å" /> | ||
'''Crystal structure of a potent small molecule inhibitor bound to cathepsin K'''<br /> | '''Crystal structure of a potent small molecule inhibitor bound to cathepsin K'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==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. | 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:[[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 NFT as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds 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:// | + | 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 superseeds 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== | ||
| Line 24: | Line 20: | ||
[[Category: structure-guided drug design]] | [[Category: structure-guided drug design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:33:04 2008'' |
Revision as of 13:33, 23 January 2008
|
Crystal structure of a potent small molecule inhibitor bound to cathepsin K
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.
About this Structure
1VSN is a Single protein structure of sequence from Homo sapiens with as ligand. This structure superseeds 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 Wed Jan 23 15:33:04 2008
