1uom

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1uom.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1uom.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1uom| PDB=1uom | SCENE= }}
{{STRUCTURE_1uom| PDB=1uom | SCENE= }}
-
'''THE STRUCTURE OF ESTROGEN RECEPTOR IN COMPLEX WITH A SELECTIVE AND POTENT TETRAHYDROISOCHIOLIN LIGAND.'''
+
===THE STRUCTURE OF ESTROGEN RECEPTOR IN COMPLEX WITH A SELECTIVE AND POTENT TETRAHYDROISOCHIOLIN LIGAND.===
-
==Overview==
+
<!--
-
As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), tetrahydroisoquinoline derivative 27 was discovered by high throughput screening. Successive replacements of the p-F substituent of 27 by an aminoethoxy side chain and of the 1-H of the tetrahydroisoquinoline core by a 1-Me group provided analogues 19 and 20. These compounds showed potencies in a cell-based reporter gene assay (ERE assay) varying between 0.6 and 20 nM and displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line with IC(50)s in the range of 2-36 nM. The effect of N-phenyl substituents on the activity and pharmacokinetic properties of tetrahydroisoquinoline analogues was explored. As a result of this investigation, two potent derivatives bearing a p-F N-aryl group, 19c and 20c, were discovered as candidates suitable for further profiling. To gain insight into the ligand-receptor interaction, the X-ray crystallographic structure of the 1-H tetrahydroisoquinoline derivative (R)-18a in complex with ERalpha-ligand binding domain (LBD)(301)(-)(553)/C--&gt;S triple mutant was solved to 2.28 A. An overlay of this X-ray crystal structure with that reported for the complex of ERalpha-LBD(301)(-)(553)/carboxymethylated C and raloxifene (5) shows that both compounds bind to the same cleft of the receptor and display comparable binding modes, with differences being observed in the conformation of their "D-ring" phenyl groups.
+
The line below this paragraph, {{ABSTRACT_PUBMED_12825935}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 12825935 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_12825935}}
==About this Structure==
==About this Structure==
Line 41: Line 45:
[[Category: Transcription regulation]]
[[Category: Transcription regulation]]
[[Category: Zinc-finger]]
[[Category: Zinc-finger]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:30:17 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:48:38 2008''

Revision as of 00:48, 28 July 2008

Image:1uom.png

Template:STRUCTURE 1uom

THE STRUCTURE OF ESTROGEN RECEPTOR IN COMPLEX WITH A SELECTIVE AND POTENT TETRAHYDROISOCHIOLIN LIGAND.

Template:ABSTRACT PUBMED 12825935

About this Structure

1UOM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Estrogen receptor modulators: identification and structure-activity relationships of potent ERalpha-selective tetrahydroisoquinoline ligands., Renaud J, Bischoff SF, Buhl T, Floersheim P, Fournier B, Halleux C, Kallen J, Keller H, Schlaeppi JM, Stark W, J Med Chem. 2003 Jul 3;46(14):2945-57. PMID:12825935

Page seeded by OCA on Mon Jul 28 03:48:38 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1uom"
Personal tools