1yim: Difference between revisions

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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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1yim, resolution 1.90Å" />

'''Human estrogen receptor alpha ligand-binding domain in complex with compound 4'''<br />

==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==

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==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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1YIM OCA].

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==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Fitzgerald, P.M.]]

[[Category: Fitzgerald, P M.]]

[[Category: Sharma, N.]]

[[Category: CM4]]

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[[Category: transcription factor]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 20~~:20:~~30 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:42 2008''

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@@ Line 1: / Line 1: @@
-[[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="450" color="white" frame="true" align="right" spinBox="true"
 caption="1yim, resolution 1.90&Aring;" />
 '''Human estrogen receptor alpha ligand-binding domain in complex with compound 4'''<br />
 ==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==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-YIM 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YIM OCA].
+YIM 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==
@@ Line 17: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Fitzgerald, P.M.]]
+[[Category: Fitzgerald, P M.]]
 [[Category: Sharma, N.]]
 [[Category: CM4]]
@@ Line 25: / Line 24: @@
 [[Category: transcription factor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:20:30 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:42 2008''