|
|
| Line 1: |
Line 1: |
| [[Image:1w83.gif|left|200px]] | | {{Seed}} |
| | [[Image:1w83.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1w83| PDB=1w83 | SCENE= }} | | {{STRUCTURE_1w83| PDB=1w83 | SCENE= }} |
|
| |
|
| '''P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH SMALL MOLECULE INHIBITOR'''
| | ===P38 KINASE CRYSTAL STRUCTURE IN COMPLEX WITH SMALL MOLECULE INHIBITOR=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| We describe the structure-guided optimization of the molecular fragments 2-amino-3-benzyloxypyridine 1 (IC(50) 1.3 mM) and 3-(2-(4-pyridyl)ethyl)indole 2 (IC(50) 35 microM) identified using X-ray crystallographic screening of p38alpha MAP kinase. Using two separate case studies, the article focuses on the key compounds synthesized, the structure-activity relationships and the binding mode observations made during this optimization process, resulting in two potent lead series that demonstrate significant increases in activity. We describe the process of compound elaboration either through the growing out from fragments into adjacent pockets or through the conjoining of overlapping fragments and demonstrate that we have exploited the mobile conserved activation loop, consisting in part of Asp168-Phe169-Gly170 (DFG), to generate significant improvements in potency and kinase selectivity.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15658855}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15658855 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15658855}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| [[Category: Kinase]] | | [[Category: Kinase]] |
| [[Category: P38]] | | [[Category: P38]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:17:11 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:40:16 2008'' |