2qtu
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here | + | Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the synthesis of a late stage intermediate that allowed us to combine A-ring and C-ring modifications and carry out simultaneous SAR studies at both positions. Modification of both positions proved additive, maintaining affinity and improving ERbeta selectivity up to 83-fold. An X-ray cocrystal structure confirms the previously observed binding mode in ERbeta. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Dodge, J | + | [[Category: Dodge, J A.]] |
| - | [[Category: Durbin, J | + | [[Category: Durbin, J D.]] |
[[Category: Krishnan, V.]] | [[Category: Krishnan, V.]] | ||
| - | [[Category: Norman, B | + | [[Category: Norman, B H.]] |
| - | [[Category: Richardson, T | + | [[Category: Richardson, T I.]] |
[[Category: Wang, Y.]] | [[Category: Wang, Y.]] | ||
[[Category: 3AS]] | [[Category: 3AS]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:42:13 2008'' |
Revision as of 16:42, 21 February 2008
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Estrogen receptor beta ligand-binding domain complexed to a benzopyran ligand
Overview
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the synthesis of a late stage intermediate that allowed us to combine A-ring and C-ring modifications and carry out simultaneous SAR studies at both positions. Modification of both positions proved additive, maintaining affinity and improving ERbeta selectivity up to 83-fold. An X-ray cocrystal structure confirms the previously observed binding mode in ERbeta.
About this Structure
2QTU is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: Combined A- and C-ring structure-activity relationship studies., Richardson TI, Dodge JA, Wang Y, Durbin JD, Krishnan V, Norman BH, Bioorg Med Chem Lett. 2007 Oct 15;17(20):5563-6. Epub 2007 Aug 11. PMID:17804226
Page seeded by OCA on Thu Feb 21 18:42:13 2008
Categories: Homo sapiens | Single protein | Dodge, J A. | Durbin, J D. | Krishnan, V. | Norman, B H. | Richardson, T I. | Wang, Y. | 3AS | Alternative splicing | Dna-binding | Ligand-binding domain | Lipid-binding | Metal-binding | Nuclear receptor | Nucleus | Phosphorylation | Steroid-binding | Transcription | Transcription regulation | Transcription regulator | Zinc | Zinc-finger
