Patent ID: 7270955

Claim:
A method to identify compounds which relieve the suppression of steroid/thyroid hormone receptor activity caused by a co-suppressor having a structure and function characteristic of a silencing mediator for retinoic acid and thyroid hormone receptors, thereby activating said receptor, said method comprising: determining the effect of a test compound on a reporter signal produced by a first expression system and on a reporter signal produced by a second expression system, wherein said first expression system comprises a complex comprising: a homodimeric or heterodimeric member of the steroid/thyroid hormone superfamily of receptors selected from thyroid hormone receptor homodimer, thyroid hormone receptor-retinoid X receptor heterodimer, retinoic acid receptor homodimer, or retinoic acid receptor-retinoid X receptor heterodimer, a response element for said member of the steroid/thyroid hormone superfamily of receptors, wherein said response element is operatively linked to a reporter, and said co-suppressor, wherein said co-suppressor comprises amino acid residues 1-1329 plus 1376-1495, as set forth in SEQ ID NO:1, or conservative amino acid variations thereof and, wherein said co-suppressor forms a complex with at least one member of the stcroi˜Jthyroid hormone superfamily of receptors and wherein said second expression system comprises a complex comprising: a homodimeric or heterodimeric form of the same member of the steroid/thyroid hormone superfamily of receptors as employed in said first expression system, wherein said member is mutated such that it retains hormone dependent activation activity but has lost its ability to repress basal level promoter activity of target genes, the same response element-reporter combination as employed in said first expression system, and said co-suppressor wherein said co-suppressor comprises amino acid residues 1-1329 plus 1376-1495, as set forth in SEQ ID NO:1, or conservative amino acid variations thereof and, wherein said co-suppressor forms a complex with at least one member of the steroid/thyroid hormone superfamily of receptors, and thereafter selecting those compounds which provide: increased reporter signal upon exposure of said compound to said second expression system, relative to reporter signal in the absence of said compound, and increased reporter signal upon exposure of said compound to said first expression system, relative to reporter signal in the absence of said compound, wherein said selected compounds are capable of relieving the suppression of steroid/thyroid hormone receptor activity caused by a co-suppressor of steroid/thyroid hormone receptor activity, said co-suppressor having a structure and function characteristic of the silencing mediator for retinoic acid and thyroid hormone receptors, and activating said receptor.