Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1.

  title={Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1.},
  author={Maria A. Bednarek and Donna L. Hreniuk and Carina P. Tan and Oksana C. Palyha and Douglas J. Macneil and Lex H. T. van der Ploeg and Andrew D. Howard and Scott D. Feighner},
  volume={41 20},
Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of Ac-Arg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Gly(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)-Pro(15)-Cys(16))-NH(2), a high affinity but nonselective agonist at hMCH-1R and hMCH-2R, were… Expand
S38151 [p-guanidinobenzoyl-[Des-Gly10]-MCH(7-17)] is a potent and selective antagonist at the MCH1 receptor and has anti-feeding properties in vivo
It is reported that S38151 antagonizes food intake when injected intra-cerebroventricularly in the rat, in agreement with the in vitro data and with the previous demonstration of a good correlation between in vitro and in vivo data on MCH(1) agonists. Expand
Small-Molecule Melanin-Concentrating Hormone-1 Receptor Antagonists Require Brain Penetration for Inhibition of Food Intake and Reduction in Body Weight
The data clearly demonstrate that MCH1R antagonists need access to the brain to reduce body weight and fat mass, and show the utility of a medicinal chemistry approach to address an important biological and pharmacological question. Expand
Cellular models for the study of the pharmacology and signaling of melanin-concentrating hormone receptors
An update is presented on the different cellular models currently used for the analysis of MCH receptor interaction and signaling and on the types of model system used for screening of novel compounds. Expand
Development of a potent and selective GPR7 (NPBW1) agonist: a systematic structure–activity study of neuropeptide B
Neuropeptide B (NPB) has been recently identified as an endogenous ligand for GPR7 (NPBW1) and GPR8 (NPBW2) and has been shown to possess a relatively high selectivity for GPR7. In order to identifyExpand
Melanin-concentrating hormone receptor antagonists as potential antiobesity agents
Pharmacological evidence supports the use of melanin-concentrating hormone receptor 1 (MCH1R) as an important receptor for mediating the effects of MCH on appetite and body weight and reports of such drug-like molecules suggest that inhibitors of M CH1R may soon be investigated as therapeutics for obesity in clinical trials. Expand
ABSTRACT Melanin-concentrating hormone (MCH) is a potent orexigenic neuropeptide and a physiological antagonist of α-melanocyte-stimulating hormone (α-MSH) in the brain as well as at peripheralExpand
Comparative autoradiographic in vitro investigation of melanin concentrating hormone receptor 1 ligands in the central nervous system.
The in vitro autoradiographic study of the unlabeled compounds SNAP-7941 and FE@SNAP further qualifies the potential of the PET-tracers [(11)C]SNAP-79 41 and [(18)F]FE@ SNAP as useful MCHR1 PET- Tracers. Expand
Discovery and development of melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity
  • L. Rokosz
  • Medicine, Biology
  • Expert opinion on drug discovery
  • 2007
This review highlights the discovery and development of multiple structural classes of MCH1 small-molecule antagonists that show impressive levels of efficacy in rodent models of obesity and why these compounds are unable to progress to the clinic due to selectivity issues. Expand
Expression and characterization of melanin-concentrating hormone receptors on mammalian cell lines
Human and other mammalian cell lines with which MCH receptor activation can be studied under "natural" conditions are described and the characteristics and signaling pathways of the MCH receptors in the different cell systems are summarized. Expand
Caractérisation des récepteurs de l'hormone de mélano-concentration (MCH)
Stable and potent MCH radioligands were developed and applied and demonstrated that MCH receptor subtypes expressed on different cell lines display different ligand recognition profiles and hence require different types ofRadioligand for binding analysis. Expand


[125I]‐S36057: a new and highly potent radioligand for the melanin‐concentrating hormone receptor
S36057 is a more potent and more stable radioligand than [125I]‐[3‐iodo Tyr13]‐MCH that will represent a reliable tool for binding assays in the search of novel MCH ligands and should provide great help for autoradiographic studies of the MCH receptor distribution in the central nervous system. Expand
Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor.
Quantitative polymerase chain reaction analysis of theSLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. Expand
An automated aequorin luminescence-based functional calcium assay for G-protein-coupled receptors.
An automated and highly sensitive functional assay for calcium-coupled receptors utilizing coelenterazine-charged aequorin as a probe for intracellular calcium levels is described and will greatly simplify the functional analysis of GPCRs and other receptors which when activated result in increases in [Ca(2+)](i). Expand