Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof
AssigneeArena Pharmaceuticals, Inc.
InventorsDominic P. Behan, Derek T. Chalmers, Chen W. Liaw, Joseph F. Russo, William J. Thomsen
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Abstract
Disclosed herein are non-endogenous, constitutively activated forms of the human 5-HT2A and human 5-HT2C receptors and uses of such receptors to screen candidate compounds. Further disclosed herein are candidate compounds identified by the screening method which act at the 5HT2A receptors. Yet further disclosed is a new class of compounds which act at the 5HT2A receptors.
Claims13
A cDNA encoding a constitutively active, non-endogenous version, of a human 5HT2C serotonin receptor comprising SEQ. ID NO. 28.
A constitutively active non-endogenous human 5HT2C serotonin receptor encoded by the cDNA of SEQ ID NO. 28 comprising SEQ ID NO. 29.
A cDNA encoding a constitutively active, non-endogenous version, of a human 5HT2A serotonin receptor comprising SEQ. ID NO. 30.
A constitutively active non-endogenous human 5HT2A serotonin receptor encoded by the cDNA of SEQ ID NO. 30 comprising SEQ ID NO. 31.
A cDNA encoding a constitutively active, non-endogenous version, of a human 5HT2A serotonin receptor comprising SEQ. ID NO. 32.
A constitutively active non-endogenous human 5HT2A serotonin receptor encoded by the cDNA of SEQ ID NO. 32 comprising SEQ ID NO. 33.
A method for identifying whether a candidate compound is an inverse agonist to a non-endogenous human 5HT2 serotonin receptor comprising the steps of:
- a. contacting the candidate compound with a non-endogenous human 5HT2 serotonin receptor;
- and
- b. determining, by measurement of a second messenger response whether said compound is an inverse agonist.
A reagent for screening compounds to determine whether the compounds are inverse agonists at human 5HT2 serotonin receptors comprising a membrane fraction from mammalian cells transfected with and expressing a cDNA encoding for a constitutively active, non-endogenous version, of a human 5HT2 serotonin receptor in which the constitutively active non-endogenous human 5HT2 receptor is expressed on the cell surface.
A reagent for screening compounds to determine whether the compounds are inverse agonists at human 5HT2 serotonin receptors comprising mammalian cells which produce a second messenger response, transfected with and expressing a cDNA encoding for a constitutively active, non-endogenous version, of a human 5HT2 serotonin receptor in which the constitutively active non-endogenous human 5HT2 receptor is expressed on the cell surface.
Dependencies are inferred from the claim text.