Abstract: Disclosed is a compound of Formula I or a salt thereof, in which X, X1, X2, R1, R2, and R3 are described herein. Also disclosed are pharmaceutical compositions and methods of using the compounds of Formula I to treat disorders mediated by melanocortin-4 receptors.

Abstract: The present invention relates to a novel biosensor. A resonance energy transfter (RET) biosensor comprising a beta(?)-arrestin tagged with a first and a second chromophore, wherein said first chromophore is a fluorophore and said second chromophore is a fluorophore or a bioluminophore is described.

Abstract: An intramolecular bioluminescence resonance energy transfer (BRET), biosensor for monitoring receptor activity and signalling cascades is disclosed. The “double-brilliance” biosensor sandwiches ?-arrestin (?-arr) between Renilla luciferase (Luc) and the yellow fluorescent protein (YFP). ?-arr associates with G-protein coupled receptors GPCR following receptor activation, bringing Luc and YPF into close proximity that favours energy transfer. In addition to providing new insights into the agonist-induced conformational rearrangements of ?-arr in living cells, the double-brilliance ?-arr offers a universal biosensor for GPCR activation, allowing the study of native receptors in large-scale screening analysis. The activity of other signalling molecules known to interact with ? arrestin could also be monitored by double brilliance ? arr.

Abstract: The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.

Abstract: The present invention relates to novel biosensors that are based on bioluminescence resonance energy transfer (BRET). These biosensors may be used to monitor rapid interaction and conformational changes within G protein-coupled receptor/G protein complexes and, in this way, reflect the activation status of the receptor. Advantageously, the biosensors may be used as a highly sensitive and quantitative assay for the identification of ligands (agonists, antagonists, inverse agonists, partial agonists, etc.) targeting G protein-coupled receptors (GPCRs) as well as for the analysis of the activation status of these receptors. Moreover, multiplexing different biosensors within receptors/G protein complexes allows for mapping ligand textures. Additionally, the biosensors permit the direct, real-time examination of interactions between receptors and G protein in their natural environment, the living cell.

Abstract: An intramolecular bioluminescence resonance energy transfer (BRET), biosensor for monitoring receptor activity and signalling cascades is disclosed. The “double-brilliance” biosensor sandwiches ?-arrestin (?-arr) between Renilla luciferase (Luc) and the yellow fluorescent protein (YFP). ?-arr associates with G-protein coupled receptors GPCR following receptor activation, bringing Luc and YPF into close proximity that favours energy transfer. In addition to providing new insights into the agonist-induced conformational rearrangements of ?-arr in living cells, the double-brilliance ?-arr offers a universal biosensor for GPCR activation, allowing the study of native receptors in large-scale screening analysis. The activity of other signalling molecules known to interact with ? arrestin could also be monitored by double brilliance ? arr.

Abstract: The present invention describes a method for producing membrane receptors based on a baculovirus/insect cell system. The invention further includes the receptors produced by the method described herein, a model for studying the properties of these membrane receptors and an assay to screen molecules that are active on these membrane receptors.

Abstract: The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.

Abstract: A method of determining whether a membrane receptor expressed in recombinant extracellular baculoviruses is active, the method comprising: providing recombinant extracellular baculoviruses expressing a membrane receptor; contacting the extracellular baculoviruses with a ligand to the membrane receptor; and determining whether binding of the ligand to the receptor occurs, wherein said binding is an indication that the receptor is active.

Abstract: Method of producing a recombinant membrane receptor protein by introducing a baculovirus expression vector encoding the membrane receptor protein into a host cell, culturing the resultant host cell for a sufficient time to permit expression of the membrane receptor protein and baculovirus viral particles and separating the cells from the viral particles. The baculovirus viral particles are then recovered.

Abstract: The present invention relates to a method for producing membrane receptors based on a baculovirus/insect cell system. The invention further includes the receptors produced by the method described herein, a model for studying the properties of these membrane receptors and an assay to screen molecules that are active on these membrane receptors.

Abstract: Method for producing membrane receptors based on a baculovirus/insect cell system. The invention further includes the receptors produced by the method described herein, a model for studying the properties of these membrane receptors and an assay to screen molecules that are active on these membrane receptors.

Abstract: Aqueous liquid detergent compositions containing a peracid and an effervesent system, wherein the effervescent system includes a first effervescent agent-containing component and a second acid agent-containing component, and the effervescent agent-containing component and the acid agent-containing component are chemically and/or physically separated from one another until effervescence is desired. Methods of laundering fabrics with such compositions.

Abstract: A lace device for tightening or closing an article such as a boot upper, garment, or backpack including a lace and at least two series of at least one guide for said lace, the sub-assembly constituted by the guides and the lace(s) defining a lacing zone, in the vicinity of which a blocking zone is located, in the area where the lace(s) extends from the lacing zone, the device further including a blocking element, a pocket adapted to receive the blocking element, the pocket being located in the blocking zone, and the pocket including passage(s) for the lace enabling the penetration of the lace between its exit from the lacing zone and its entry into the blocking element.

Abstract: A lace device for tightening or closing an article such as a boot upper, garment, or backpack including a lace and at least two series of at least one guide for said lace, the sub-assembly constituted by the guides and the lace(s) defining a lacing zone, in the vicinity of which a blocking zone is located, in the area where the lace(s) extends from the lacing zone, the device further including a blocking element, a pocket adapted to receive the blocking element, the pocket being located in the blocking zone, and the pocket including passage(s) for the lace enabling the penetration of the lace between its exit from the lacing zone and its entry into the blocking element.