Detection system and uses therefor

A method for determining whether and/or the extent to which a test compound interacts with a second protein when the second protein is associated with a first protein, the method characterised in that the first and second proteins are both receptors, and the method comprises a method for screening a test compound for first protein/second protein hetero-dimer/-oligomer selective antagonism or partial agonism, the method comprising the steps of:

• a) determining whether, and/or the extent to which, the test compound is an antagonist or partial agonist of the first protein/second protein hetero-dimer/-oligomer, by contacting said test compound with a system comprising:
• i) a first agent, comprising the second protein coupled to a first reporter component;
• ii) a second agent, comprising an interacting group coupled to a second reporter component;
• iii) a third agent, comprising the first protein;
• iv) an agonist of the second protein, the first protein and/or the first protein/second protein hetero-dimer/-oligomer,
• wherein proximity of the first and second reporter components generates a signal, and wherein a modulator modulates association of the interacting group with the first protein;
• b) detecting a decrease in the signal as a determination of whether and/or the extent to which the test compound is an antagonist or partial agonist of the first protein/second protein hetero-dimer/-oligomer;
• and
• c) if the test compound is an antagonist or partial agonist of the first protein/second protein hetero-dimer/-oligomer, determining whether, and/or the extent to which the test compound is an antagonist or partial agonist of the first protein in the absence of the second protein and the second protein in the absence of the first protein;
• such that a test compound that exhibits greater antagonistic or partial agonistic properties when interacting with the first protein/second protein hetero-dimer/-oligomer is selective for the first protein/second protein hetero-dimer/-oligomer.

A method for determining whether and/or the extent to which a test compound interacts with a second protein when the second protein is associated with a first protein, the method characterised in that the first and second proteins are both receptors, and the method comprises a method for screening a test compound for first protein/second protein hetero-dimer/-oligomer selective inverse agonism, the method comprising the steps of:

• a) determining whether, and/or the extent to which, the test compound is an inverse agonist of the first protein/second protein hetero-dimer/-oligomer, by contacting said test compound with a system comprising:
• i) a first agent, comprising the second protein coupled to a first reporter component;
• ii) a second agent, comprising an interacting group coupled to a second reporter component;
• iii) a third agent, comprising the first protein, wherein the first protein is constitutively active, and wherein proximity of the first and second reporter components generates a signal, and wherein a modulator modulates association of the interacting group with the first protein;
• b) detecting a decrease in the signal as a determination of whether and/or the extent to which the test compound is an inverse agonist of the first protein/second protein hetero-dimer/-oligomer;
• and
• c) if the test compound is an inverse agonist of the first protein/second protein hetero-dimer/-oligomer, determining whether, and/or the extent to which the test compound is an inverse agonist of the second protein in the absence of the first protein and the first protein in the absence of the second protein;
• such that the test compound that exhibits greater inverse agonistic properties when interacting with the first protein/second protein hetero-dimer/-oligomer is selective for the first protein/second protein hetero-dimer/-oligomer.