Novel estrogen receptor ligand binding domain variants and novel ligands and pharmaceutical compositions
AssigneeNovartis AG
InventorsKathryn Rene Bracken, Joseph Ernest de los Angeles, Ying Huang, Michael Joseph Kadan, Gary Michael Ksander, Dennis Bryan Zerby
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Abstract
Mutants of steroid receptor ligand binding domains and synthetic ligands which have specific binding affinities for these receptors are provided. The use of these LBD-ligand combinations for construction of selective “molecular gene switches” is disclosed. Methods of regulating gene function using these switches are provided.
Claims70
A modified estrogen receptor alpha ligand binding domain comprising at least one amino acid modification in Region 1, at least one amino acid modification in Region 2, or at least one amino acid modification in each of both Regions 1 and 2, wherein said ligand binding domain interacts with a non-endogenous ligand as a result of said at least one amino acid modification.
The compound LBB938 which is 4-((1Z))-3-bicyclo[hept-2-yl-1-{4-[2-(dimethylamino)ethoxy]phenyl}-2-phenylprop-1-enyl)phenol, the structure of which is
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The compound LBF580 4-((1E)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-2-(4-morpholin-4- ylphenyl)prop-1-enyl)phenol, the structure of which is
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The compound LBB551, carbamic acid, [(2Z)-3-[4-[2-(dimethylamino)ethoxy]phenyl]-3-(4-hydroxyphenyl)-2-phenyl-2-propenyl]-, methyl ester, the structure of which is
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The compound LBC081, carbamic acid, [(2E)-3-[4-[2-(dimethylamino)ethoxy]phenyl]-3-(4-hydroxyphenyl)-2-phenyl-2-propenyl]-, methyl ester, the structure of which is
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Dependencies are inferred from the claim text.