1vsn

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[[Image:1vsn.jpg|left|200px]]<br /><applet load="1vsn" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1vsn.jpg|left|200px]]
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caption="1vsn, resolution 2.000&Aring;" />
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'''Crystal structure of a potent small molecule inhibitor bound to cathepsin K'''<br />
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{{Structure
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|PDB= 1vsn |SIZE=350|CAPTION= <scene name='initialview01'>1vsn</scene>, resolution 2.000&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NFT:N-(2-AMINOETHYL)-N~2~-{(1S)-1-[4'-(AMINOSULFONYL)BIPHENYL-4-YL]-2,2,2-TRIFLUOROETHYL}-L-LEUCINAMIDE'>NFT</scene>
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|ACTIVITY= [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]
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|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal structure of a potent small molecule inhibitor bound to cathepsin K'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1VSN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 2FDZ. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VSN OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16413777 16413777]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16413777 16413777]
[[Category: Cathepsin K]]
[[Category: Cathepsin K]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: structure-guided drug design]]
[[Category: structure-guided drug design]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:49:13 2008''

Revision as of 12:49, 20 March 2008

Image:1vsn.jpg


PDB ID 1vsn

Drag the structure with the mouse to rotate
, resolution 2.000Å
Ligands:
Gene: CTSK, CTSO, CTSO2 (Homo sapiens)
Activity: Cathepsin K, with EC number 3.4.22.38
Coordinates: save as pdb, mmCIF, xml



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. This structure supersedes the now removed PDB entry 2FDZ. 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

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