Method for identifying modulators of GPCR GPR1 function
AssigneeActelion Pharmaceuticals Ltd.
InventorXavier Leroy
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Abstract
The invention relates to the identification of Humanin and derivatives thereof as ligands of the GPR1 GPCR (G-protein coupled receptor). The invention encompasses the use of the interaction of GPR1 polypeptides and Humanin polypeptides as the basis of screening assays for agents that modulate the activity of the GPR1 receptor. The invention also encompasses diagnostic assays based upon the GPR1/Humanin polypeptide interaction, as well as kits for performing diagnostic and screening assays.
Claims32
A method of identifying an agent that modulates the function of GPR1, the method comprising:
- a) contacting a GPR1 polypeptide with a Humanin polypeptide in the presence or absence of a candidate modulator under conditions permitting the interaction of the Humanin polypeptide with the GPR1 polypeptide;
- and
- b) measuring the interaction of the GPR1 polypeptide with the Humanin polypeptide, wherein an increase or a decrease in interaction in the presence of the candidate modulator, relative to the interaction in the absence of the candidate modulator, identifies the candidate modulator as an agent that modulates the function of GPR1;
- wherein the Humanin polypeptide is a polypeptide having at least 95% sequence identity to polypeptides of SEQ ID NO:
- 12, 13, 14 or 15 that specifically binds to and/or activates a signaling activity of a GPR1 polypeptide having the sequence of SEQ ID NO:
- 2.
A method of identifying an agent that modulates the function of GPR1, the method comprising:
- a) contacting a GPR1 polypeptide with a Humanin polypeptide in the presence or absence of a candidate modulator under conditions permitting the interaction of the Humanin polypeptide with the GPR1 polypeptide;
- and
- b) measuring a signaling activity of the GPR1 polypeptide, wherein a change in the activity in the presence of the candidate modulator relative to the activity in the absence of the candidate modulator identifies the candidate modulator as an agent that modulates the function of GPR1;
- wherein the Humanin polypeptide is a polypeptide having at least 95% sequence identity to polypeptides of SEQ ID Nos:
- 12, 13, 14 or 15 that specifically binds to and/or activates a signaling activity of a GPR1 polypeptide having the sequence of SEQ ID No:
- 2.
A method of identifying an agent that modulates the function of GPR 1, the method comprising:
- a) contacting a GPR1 polypeptide with a candidate modulator;
- b) measuring a signaling activity of the GPR1 polypeptide in the presence of the candidate modulator;
- and
- c) comparing the activity measured in the presence of the candidate modulator to the activity measured in a sample in which the GPR1 polypeptide is contacted with a Humanin polypeptide, wherein the candidate modulator is identified as an agent that modulates the function of GPR1 when the amount of the activity measured in the presence of the candidate modulator is at least 50% of the amount induced by the Humanin polypeptide present at its EC50;
- wherein the Humanin polypeptide is a polypeptide having at least 95% identity to polypeptides of SEQ ID NOs:
- 12, 13, 14 or 15 that specifically binds to and/or activates a signaling activity of a GPR1 polypeptide having the sequence of SEQ ID NO:
- 2.
The method according to claim I, wherein measuring the interaction of the GPR1 polypeptide with the Humanin polypeptide with the candidate modulator is measured relative to the interaction in the absence of the candidate modulator.
Dependencies are inferred from the claim text.