Assay for and uses of peptide hormone receptor ligands

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/16 (2006.01) A61K 31/55 (2006.01) C07K 14/72 (2006.01) C12Q 1/02 (2006.01) G01N 33/566 (2006.01) G01N 33/74 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2239293

The invention features a method for determining whether a candidate compound is a non-peptide agonist of a peptide hormone receptor. In this method, a candidate compound is exposed to a form of the peptide hormone receptor which has an enhanced ability to amplify the intrinsic activity of a non-peptide agonist. The second messenger signaling activity of the enhanced receptor is measured in the presence of the candidate compound, and compared to the second messenger signaling activity of the enhanced receptor measured in the absence of the candidate compound. A change in second messenger signaling activity indicates that the candiate compound is an agonist. An increase in second messenger signaling activity indicates that the compound is either a full or partial agonist; a decrease in second messenger signaling activity indicates that the compound is an inverse agonist.

L'invention se rapporte à un procédé visant à déterminer si un composé candidat est un agoniste non peptidique d'un récepteur d'hormone peptidique. Dans ce procédé, un composé candidat est exposé à une forme de récepteur d'hormone peptidique présentant une meilleure capacité à intensifier l'activité intrinsèque d'un agoniste non peptidique. L'activité signalant un second messager du récepteur à capacité améliorée est mesurée en présence d'un composé candidat et comparée à l'activité signalant un second messager du récepteur à capacité améliorée mesurée en l'absence du composé candidat. Une modification de l'activité signalant un second messager indique que le composé candidat est un agoniste. Une augmentation de l'activité signalant un second messager indique que le composé est soit un agoniste complet, soit un agoniste partiel; une diminution de l'activité signalant un second messager indique que le composé est un agoniste inverse.

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