Methods and systems for modulating hormones and related methods, agents and compositions
AssigneesCalifornia Institute of Technology, The Regents of the University of California, The United States of America as represented by the Department of Veterans Affairs
InventorsWilliam A. GODDARD, III, Mark MENNA, Stephen PANDOL, Ravinder ABROL
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Abstract
Provided herein are bitter taste receptor ligands, related agents, combinations, compositions, methods and systems for modulating release of a metabolic hormone in vitro or in vivo from cells of the GI tract of an individual.
Claims39
A method for modulating release of a metabolic hormone in an individual, the method comprising
- administering to the individual one or more GI bitter taste receptor ligands selected from PTU, PTC, denatonium benzoate, Glycyrrhizic acid ammonium salt, Epigallocatechin gallate, Hyperforin, Berberine chloride, Coptisine Chloride, Allyl methyl sulfide, Rottlerin, Curcumin, Ellagic acid, Embelin and/or or a derivative thereof, in an effective amount to allow binding of the one or more GI bitter taste receptor ligands to the one or more GI bitter taste receptors in the individual, the binding resulting in modulating release of metabolic hormone GLP-1, PYY and/or CCK.
A composition for modulating release of a metabolic hormone in an individual, the composition comprising one or more GI bitter taste receptor ligands selected from PTU, PTC, denatonium benzoate, Glycyrrhizic acid ammonium salt, Epigallocatechin gallate, Hyperforin, Berberine chloride, Coptisine Chloride, Allyl methyl sulfide, Rottlerin, Curcumin, Ellagic acid, Embelin and/or or a derivative thereof together with a suitable vehicle.
A bitter tastant agent for modulating a target bitter tastant receptor, the bitter tastant agent comprising a bitter taste receptor ligand conjugated to a complementary molecule configured for interfering with systemic absorption and release of the bitter taste receptor ligand,
- wherein the bitter taste receptor ligand comprises a first portion and a second portion, the first portion active with respect to the binding of the bitter taste receptor ligand to the bitter taste receptor and the second portion passive with respect to the binding of the bitter taste receptor ligand to the bitter taste receptor, and
- wherein the complementary molecule is attached to the second portion of the bitter taste receptor ligand to provide the bitter tastant agent configured to present the first portion of the bitter taste receptor ligand for binding to the bitter taste receptor agent.
A bitter tastant agent comprising a bitter tastant receptor ligand conjugated with a complementary molecule, wherein the complementary molecule is configured for interfering with systemic release of the bitter tastant receptor ligand.
A method for modulating release of a metabolic hormone and a related biological process thereof in an individual, the method comprising
- administering to the individual an effective amount of one or more agents to activate one or more bitter taste receptors in the individual.
A method to identify a biological response associated to activation of a bitter tastant receptor in a cell, the method comprising
- contacting the cell with one or more bitter tastant receptor ligands selected PTU, PTC, denatonium benzoate, Glycyrrhizic acid ammonium salt, Epigallocatechin gallate, Hyperforin, Berberine chloride, Coptisine Chloride Allyl methyl sulfide, Rottlerin, Curcumin, Ellagic acid, Embelin and a derivative thereof to allow binding of the bitter tastant receptor ligand to the bitter tastant receptor;
- and
- detecting the biological response in the cell following the contacting.
A method to identify a GI bitter taste receptor ligand capable of modulating release of metabolic hormones associated to the GI system, the method comprising
- identifying a GI bitter taste receptor that is expressed in a target cell in the GI system;
- predicting the structure of the GI bitter tastant receptor,
- identifying a candidate ligand that binds to the GI bitter tastant receptor based on the predicted GI bitter tastant receptor structure,
- testing the identified candidate ligand in a bitter taste receptor activation assay, and
- testing effect of the candidate ligand on a modulation of at least one of the metabolic hormones associated with the GI system.
A method to modulate hormone release from a cell, the method comprising
- inducing a specific conformation of a GI bitter tastant receptor through binding of a GI bitter taste receptor ligand, the specific conformation being at least one of a plurality of active conformations of the GI bitter tastant receptor;
- detecting increase or decrease of hormone release from a cell following the inducing;
- and
- modulating said increase or decrease through action of the GI bitter taste receptor ligand.
A method to treat or prevent in an individual a condition associated to a metabolic hormone, the method comprising
- administering to the individual one or more GI bitter taste receptor ligands selected from PTU, PTC, denatonium benzoate, Glycyrrhizic acid ammonium salt, Epigallocatechin gallate, Hyperforin, Berberine chloride, Coptisine Chloride Allyl methyl sulfide, Rottlerin, Curcumin, Ellagic acid, and Embelin and a derivative thereof, in a therapeutically effective amount to modulate metabolic hormone GLP-1, PYY and/or CCK.
Dependencies are inferred from the claim text.