1vsn
From Proteopedia
| Line 5: | Line 5: | ||
|SITE= | |SITE= | ||
|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> | |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> | ||
| - | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vsn OCA], [http://www.ebi.ac.uk/pdbsum/1vsn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vsn RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==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== | ||
| Line 27: | Line 27: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: McGrath, M.]] | [[Category: McGrath, M.]] | ||
| - | [[Category: NFT]] | ||
[[Category: osteoporosis]] | [[Category: osteoporosis]] | ||
[[Category: proteae]] | [[Category: proteae]] | ||
[[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 Mon Mar 31 00:28:12 2008'' |
Revision as of 21:28, 30 March 2008
| |||||||
| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CTSK, CTSO, CTSO2 (Homo sapiens) | ||||||
| Activity: | Cathepsin K, with EC number 3.4.22.38 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 00:28:12 2008
