1yim
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= ESR1, ESR, NR3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ESR1, ESR, NR3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1yin|1YIN]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yim OCA], [http://www.ebi.ac.uk/pdbsum/1yim PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yim RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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). | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Fitzgerald, P M.]] | [[Category: Fitzgerald, P M.]] | ||
[[Category: Sharma, N.]] | [[Category: Sharma, N.]] | ||
| - | [[Category: CM4]] | ||
[[Category: antagonist]] | [[Category: antagonist]] | ||
[[Category: er-alpha]] | [[Category: er-alpha]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''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 01:08:36 2008'' |
Revision as of 22:08, 30 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ESR1, ESR, NR3A1 (Homo sapiens) | ||||||
| Related: | 1YIN
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human estrogen receptor alpha ligand-binding domain in complex with compound 4
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).
About this Structure
1YIM is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 01:08:36 2008
