Biased Ligands for Receptors Such as the PTH Receptor
OwnerLouis Luttrell, Robert Lefkowitz +1inventors
InventorsLouis Luttrell, Robert Lefkowitz, Diane Gesty-Palmer
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Abstract
Disclosed are compositions and methods for modulating the β-arrestin pathway selectively over the G protein pathway of a G protein couple receptor, such as parathyroid hormone receptor.
Claims20
A method of modulating a seven transmembrane receptor, comprising contacting a seven transmebrane receptor with a biased ligand.
The method of claim 13, wherein the biased ligand does not increase osteoclast recruitment relative to a control.
The method of claim 13, wherein the biased ligand does not increase osteoclast differentiation relative to a control.
The method of claim 19, wherein the subject has a bone disorder.
The method of claim 20, wherein the bone disorder is osteoporosis.
The method of claim 19, wherein the modulation of the seven transmebrane receptor is monitored by the step of analyzing a biofluid of the subject for markers indicating biased ligand modulation.
The method of claim 22, wherein the non-biased ligand comprises PTH.
A method of analyzing activity of a composition comprising, a) contacting the composition with a GPCR, b) determining the activation of a first signal transduction pathway of the GPCR, producing a first activation result, c) determining the activation of a second signal transduction pathway of the GPCR, producing a second activation result, and wherein the first activation result and the second activation result produce an activity profile of the composition.
The method of claim 30, wherein the GPCR is PTH1R.
The method of claim 30, wherein method further comprises d) contacting the GPCR with a control e) determining the activation of a first signal transduction pathway of the GPCR, producing a first activation control result, f) determining the activation of a second signal transduction pathway of the GPCR, producing a second activation control result, and wherein the first activation control result and the second activation control result produce an activity profile of the composition.
Dependencies are inferred from the claim text.