1yim
From Proteopedia
(New page: 200px<br /> <applet load="1yim" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yim, resolution 1.90Å" /> '''Human estrogen rece...) |
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| - | [[Image:1yim.gif|left|200px]]<br /> | + | [[Image:1yim.gif|left|200px]]<br /><applet load="1yim" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yim" size=" | + | |
caption="1yim, resolution 1.90Å" /> | caption="1yim, resolution 1.90Å" /> | ||
'''Human estrogen receptor alpha ligand-binding domain in complex with compound 4'''<br /> | '''Human estrogen receptor alpha ligand-binding domain in complex with compound 4'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The discovery, synthesis, and SAR of chromanes as ER alpha subtype | + | The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs). |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YIM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CM4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YIM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CM4:'>CM4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YIM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fitzgerald, P | + | [[Category: Fitzgerald, P M.]] |
[[Category: Sharma, N.]] | [[Category: Sharma, N.]] | ||
[[Category: CM4]] | [[Category: CM4]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:42 2008'' |
Revision as of 14:05, 21 February 2008
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Human estrogen receptor alpha ligand-binding domain in complex with compound 4
Contents |
Overview
The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).
Disease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this Structure
1YIM is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs., Tan Q, Blizzard TA, Morgan JD 2nd, Birzin ET, Chan W, Yang YT, Pai LY, Hayes EC, DaSilva CA, Warrier S, Yudkovitz J, Wilkinson HA, Sharma N, Fitzgerald PM, Li S, Colwell L, Fisher JE, Adamski S, Reszka AA, Kimmel D, DiNinno F, Rohrer SP, Freedman LP, Schaeffer JM, Hammond ML, Bioorg Med Chem Lett. 2005 Mar 15;15(6):1675-81. PMID:15745820
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