1vjy
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=460:2-[5-(6-METHYLPYRIDIN-2-YL)-2,3-DIHYDRO-1H-PYRAZOL-4-YL]-1,5-NAPHTHYRIDINE'>460</scene> | |LIGAND= <scene name='pdbligand=460:2-[5-(6-METHYLPYRIDIN-2-YL)-2,3-DIHYDRO-1H-PYRAZOL-4-YL]-1,5-NAPHTHYRIDINE'>460</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vjy OCA], [http://www.ebi.ac.uk/pdbsum/1vjy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vjy RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies. | Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Loeys-Dietz syndrome, type 1A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]], Loeys-Dietz syndrome, type 2A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wang, R.]] | [[Category: Wang, R.]] | ||
[[Category: Woolven, J.]] | [[Category: Woolven, J.]] | ||
| - | [[Category: 460]] | ||
[[Category: inhibitor complex]] | [[Category: inhibitor complex]] | ||
[[Category: protein kinase]] | [[Category: protein kinase]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 00:25:29 2008'' |
Revision as of 21:25, 30 March 2008
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| , resolution 2.0Å | |||||||
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| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor
Overview
Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.
About this Structure
1VJY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors., Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, Janson C, Smith W, Krysa G, Boullay V, De Gouville AC, Huet S, Hartley D, J Med Chem. 2004 Aug 26;47(18):4494-506. PMID:15317461
Page seeded by OCA on Mon Mar 31 00:25:29 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Boullay, V. | Fouchet, M H. | Gellibert, F. | Goodland, H. | Gouville, A C.de. | Hartley, D. | Huet, S. | Janson, C. | Krysa, G. | Laroze, A. | Lovegrove, V. | Mathews, N. | Nguyen, V L. | Sautet, S. | Smith, W. | Wang, R. | Woolven, J. | Inhibitor complex | Protein kinase | Transferase
