1sl3: Difference between revisions
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|PDB= 1sl3 |SIZE=350|CAPTION= <scene name='initialview01'>1sl3</scene>, resolution 1.81Å | |PDB= 1sl3 |SIZE=350|CAPTION= <scene name='initialview01'>1sl3</scene>, resolution 1.81Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=170:(2-[6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDOPYRIDIN-2-YL)ETHYL]AMINO}-2-OXOPYRAZIN-1(2H)-YL]-N-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]ACETAMIDE'>170</scene> | |LIGAND= <scene name='pdbligand=170:(2-[6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDOPYRIDIN-2-YL)ETHYL]AMINO}-2-OXOPYRAZIN-1(2H)-YL]-N-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]ACETAMIDE'>170</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sl3 OCA], [http://www.ebi.ac.uk/pdbsum/1sl3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sl3 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P(1) region. Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K(i) of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P(1) aryl heterocycles with a variety of P(2)-P(3) groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P(1) will allow for more diversification in the P(2)-P(3) region to ultimately address additional pharmacological concerns. | In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P(1) region. Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K(i) of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P(1) aryl heterocycles with a variety of P(2)-P(3) groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P(1) will allow for more diversification in the P(2)-P(3) region to ultimately address additional pharmacological concerns. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Williams, P D.]] | [[Category: Williams, P D.]] | ||
[[Category: Young, M B.]] | [[Category: Young, M B.]] | ||
[[Category: thrombin inhibitor complex]] | [[Category: thrombin inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:43:29 2008'' | ||
Revision as of 23:43, 30 March 2008
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| , resolution 1.81Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor
OverviewOverview
In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P(1) region. Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K(i) of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P(1) aryl heterocycles with a variety of P(2)-P(3) groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P(1) will allow for more diversification in the P(2)-P(3) region to ultimately address additional pharmacological concerns.
About this StructureAbout this Structure
1SL3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors., Young MB, Barrow JC, Glass KL, Lundell GF, Newton CL, Pellicore JM, Rittle KE, Selnick HG, Stauffer KJ, Vacca JP, Williams PD, Bohn D, Clayton FC, Cook JJ, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Miller-Stein C, Pietrak BL, Wallace AA, White RB, Wong B, Yan Y, Nantermet PG, J Med Chem. 2004 Jun 3;47(12):2995-3008. PMID:15163182
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Thrombin
- Barrow, J C.
- Bohn, D.
- Clayton, F C.
- Cook, J J.
- Glass, K L.
- Krueger, J A.
- Kuo, L C.
- Lewis, S D.
- Lucas, B J.
- Lundell, G F.
- McMasters, D R.
- Miller-Stein, C.
- Newton, C L.
- Pellicore, J M.
- Pietrak, B L.
- Rittle, K E.
- Selnick, H G.
- Stauffer, K J.
- Vacca, J P.
- Williams, P D.
- Young, M B.
- Thrombin inhibitor complex