2qtu: Difference between revisions
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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 3AS 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
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- 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
