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1uom

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Revision as of 09:47, 30 October 2007 by OCA (Talk | contribs)
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1uom, resolution 2.28Å

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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, ... [(full description)]

About this Structure

1UOM is a [Single protein] structure of sequence from [Homo sapiens] with PTI as [ligand]. Structure known Active Site: PTI. 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

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