|
|
| Line 1: |
Line 1: |
| [[Image:1u3q.gif|left|200px]] | | {{Seed}} |
| | [[Image:1u3q.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1u3q| PDB=1u3q | SCENE= }} | | {{STRUCTURE_1u3q| PDB=1u3q | SCENE= }} |
|
| |
|
| '''Crystal Structure of Estrogen Receptor beta complexed with CL-272'''
| | ===Crystal Structure of Estrogen Receptor beta complexed with CL-272=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are >100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least approximately 50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15456246}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15456246 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15456246}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 41: |
Line 45: |
| [[Category: Nuclear receptor]] | | [[Category: Nuclear receptor]] |
| [[Category: Transcription factor]] | | [[Category: Transcription factor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:43:35 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:26:35 2008'' |