Affinage

MCHR1

Melanin-concentrating hormone receptor 1 · UniProt Q99705

Length
353 aa
Mass
38.9 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCHR1 (SLC-1/GPR24) is the cognate G protein-coupled receptor for the neuropeptide melanin-concentrating hormone (MCH), which it binds with sub-nanomolar affinity to control energy homeostasis and a range of CNS and endocrine functions (PMID:10421367, PMID:10441476). Ligand engagement requires the MCH ring structure (residues spanning MCH-6-17, with Met8, Arg11, and Tyr13 critical for full agonism), and disruption of the peptide disulfide bridge abolishes agonism (PMID:11278733). The receptor displays cell-type-dependent G-protein coupling: it engages both Gαi/o (inhibiting adenylyl cyclase and activating GIRK currents) and Gαq (mobilizing intracellular Ca2+ through PLC), with some contexts showing selective Gαi/o coupling (melanoma cells) and others selective Gαq coupling (neuronal lines) (PMID:10471841, PMID:11708774, PMID:16524757). In CNS neurons, MCHR1 is concentrated in the primary cilium, where AHI1-dependent trafficking into the cilium is required for MCH-stimulated cAMP and ERK signaling (PMID:32530066, PMID:33741721). Receptor activity is restrained by MRAP2, which physically interacts via its C-terminus to inhibit MCHR1 signaling and modulate its membrane transport (PMID:35311242). Beyond MCH, MCHR1 binds PDGF-BB directly in dermal fibroblasts and mediates PDGF-BB-driven profibrotic responses (PMID:34912333). In vivo, MCHR1 signaling tonically regulates locomotor activity, anxiety via serotonergic modulation in prefrontal cortex, cortical bone mass, and thyroid hormone secretion (PMID:15544841, PMID:15988472, PMID:15147966, PMID:23024261).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1999 High

    Deorphanized the receptor SLC-1 by establishing MCH as its cognate ligand, defining the molecular entry point for MCH signaling.

    Evidence Radioligand binding, Ca2+ and cAMP assays in HEK293/CHO cells expressing SLC-1; ligand purification from rat brain extract

    PMID:10421367 PMID:10441476

    Open questions at the time
    • Did not resolve the structural basis of MCH binding
    • Endogenous tissue distribution of the receptor not mapped
  2. 1999 High

    Demonstrated that MCHR1 couples to two distinct G-protein pathways, establishing dual signaling capacity.

    Evidence Xenopus oocyte expression with GIRK channels; electrophysiology of GIRK-mediated and Ca2+-dependent Cl- currents

    PMID:10471841

    Open questions at the time
    • Did not establish which coupling dominates in native cells
    • Determinants of pathway selection unknown
  3. 2001 High

    Mapped the minimal agonist determinants of MCH and correlated receptor pharmacology with in vivo feeding, linking MCHR1 to orexigenic action.

    Evidence cAMP inhibition and [35S]-GTPγS/radioligand assays with MCH analogue mutagenesis; ICV injection with food intake measurement

    PMID:11278733 PMID:11561073

    Open questions at the time
    • Receptor residues contacting the key MCH residues not defined
    • Did not identify the neural circuit mediating feeding
  4. 2002 Medium

    Showed that MCHR1 coupling profile is cell-context dependent and operates outside the CNS, including immune cells.

    Evidence cAMP, MAPK, Ca2+ assays with pertussis toxin in melanoma cells; cAMP/Ca2+/proliferation assays in human PBMCs

    PMID:11708774 PMID:12220661

    Open questions at the time
    • Mechanism dictating Gαi/o vs Gαq selection unresolved
    • Physiological relevance of immune signaling not tested in vivo
  5. 2012 Medium

    Defined physiological outputs of MCHR1 signaling through knockout phenotyping across bone, locomotion, anxiety, and thyroid axes.

    Evidence MCHR1/Pmch knockout mice with bone mass, wheel running, behavioral paradigms, microdialysis, and thyroid hormone secretion assays

    PMID:15147966 PMID:15544841 PMID:15988472 PMID:23024261

    Open questions at the time
    • Did not pinpoint the cell types mediating each phenotype
    • Downstream signaling linking receptor to each output not traced
  6. 2021 High

    Established ciliary localization as a requirement for MCHR1 signaling and identified AHI1 as the trafficking factor.

    Evidence Immunohistochemistry of ciliary MCHR1 across brain regions; Ahi1-/- neurons with ciliary localization, cAMP, and ERK readouts

    PMID:32530066 PMID:33741721

    Open questions at the time
    • Molecular mechanism of AHI1-mediated ciliary entry not resolved
    • Whether ciliary requirement applies to all physiological outputs untested
  7. 2022 Medium

    Identified regulatory and non-canonical partners of MCHR1: the accessory protein MRAP2 as a signaling inhibitor and PDGF-BB as a direct binding ligand in fibroblasts.

    Evidence Co-IP, BiFC and C-terminal truncation for MRAP2; SPR binding and siRNA knockdown with profibrotic gene/cAMP readouts for PDGF-BB

    PMID:34912333 PMID:35311242

    Open questions at the time
    • Structural basis of MRAP2 and PDGF-BB interactions undefined
    • In vivo relevance of PDGF-BB/MCHR1 axis not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MCHR1 selects between Gαi/o and Gαq in different cell types, and how ciliary localization and accessory proteins integrate to determine its physiological outputs, remain unresolved.
  • No structural model of agonist-bound MCHR1
  • Mechanism of cell-type-specific G-protein selection unknown
  • Link between ciliary signaling and specific in vivo phenotypes uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005929 cilium 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
AHI1MCHMRAP2PDGFB

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The orphan G-protein-coupled receptor SLC-1 (MCHR1) was identified as the cognate receptor for melanin-concentrating hormone (MCH): SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and MCH stimulates intracellular Ca2+ mobilization and reduces forskolin-elevated cAMP levels via this receptor. Radioligand binding assay, Ca2+ mobilization assay, cAMP assay in HEK293 cells expressing SLC-1 Nature High 10421367
1999 MCHR1 (SLC-1) couples to both Gi/Go (GIRK-mediated currents) and Gq (PLC-mediated Ca2+-dependent Cl- currents) signal transduction pathways when expressed in Xenopus oocytes, demonstrating dual G-protein coupling. Xenopus oocyte expression system with co-expressed GIRK channels; electrophysiological recording of GIRK-mediated and Ca2+-dependent Cl- currents after MCH stimulation; ligand isolation by cation exchange chromatography and HPLC with mass spectrometry FEBS letters High 10471841
1999 MCH was isolated and identified as the endogenous ligand of the SLC-1 receptor by purifying rat brain extracts and demonstrating dose-dependent inhibition of forskolin-stimulated cAMP accumulation in CHO cells expressing rat and human SLC-1, with EC50 of 0.2 nM for both species. HPLC purification of rat brain extract; cAMP inhibition assay in CHO cells stably expressing SLC-1 Biochemical and biophysical research communications High 10441476
2001 Structure-activity relationship studies on MCHR1 (SLC-1) identified the minimal MCH sequence required for full agonism as MCH-(6-17) (the ring structure), with residues Met8, Arg11, and Tyr13 being essential for full potency in both cAMP inhibition and [35S]-GTPγS binding assays. Disruption of the disulfide bridge by Asp/Lys substitution eliminated agonist activity and produced weak micromolar antagonists. cAMP inhibition assay and [35S]-GTPγS binding on HEK293 cells stably expressing human MCHR1; alanine scanning and deletion mutagenesis of MCH peptide analogues The Journal of biological chemistry High 11278733
2001 Agonist potencies of MCH analogues at the rat recombinant SLC-1 receptor (cAMP inhibition and radioligand binding) strongly correlated with in vivo feeding effects in rats upon intracerebroventricular injection, establishing SLC-1 as the mediator of MCH orexigenic actions. cAMP inhibition assay and [125I]S36057 binding on rat recombinant SLC-1; intracerebroventricular injection of MCH analogues with food intake measurement The Journal of pharmacology and experimental therapeutics High 11561073
2001 In SK-MEL-37 melanoma cells expressing endogenous SLC-1 (MCHR1), MCH inhibited cAMP and induced p42/p44 MAPK activation in a pertussis toxin-sensitive manner, but did not increase intracellular Ca2+, indicating selective coupling to Gαi/Gαo (not Gαq) in this cellular context. Overexpression studies in CHO and HEK293 cells confirmed SLC-1 can couple to both Gαi/Gαo and Gαq. cAMP inhibition assay, MAPK activation assay, Ca2+ mobilization assay, pertussis toxin treatment, cDNA transfection in CHO and 293 cells Biochemical and biophysical research communications High 11708774
2002 MCHR1 expressed in human peripheral blood mononuclear cells (PBMCs) couples to cAMP synthesis and calcium mobilization upon MCH stimulation, and MCH treatment decreases CD3-stimulated PBMC proliferation in vitro, indicating an immunomodulatory function of MCHR1. FACS, cAMP assay, Ca2+ mobilization assay, RT-PCR, in vitro PBMC proliferation assay FEBS letters Medium 12220661
2002 Rhesus monkey MCH-R1 binds MCH with Kd of 6.5 nM and couples through both Gi/Go and Gq-type G proteins, mirroring human MCH-R1 signaling properties. Radioligand binding assay, intracellular signaling assays in cells expressing cloned rhesus MCH-R1 Peptides Medium 12182940
2004 MCHR1-deficient mice develop osteoporosis characterized by reduced cortical bone mass and increased bone resorption (elevated serum c-telopeptide), indicating that MCHR1 signaling tonically stimulates cortical bone mass. Genetic knockout (MCHR1-/- mice), bone mass measurement, serum c-telopeptide assay Biochemical and biophysical research communications Medium 15147966
2005 Mch1r-deficient mice show enhanced voluntary wheel running activity, and Pmch-deficient mice also exhibit increased running activity, establishing that endogenous MCH acting through MCH1R inhibits locomotor activity. Naloxone suppressed wheel running in both genotypes, suggesting opioid regulation; wheel running increased dynorphin mRNA in Mch1r-/- brain. Voluntary wheel running assay in Mch1r-/- and Pmch-/- knockout mice; naloxone injection; dynorphin mRNA measurement Regulatory peptides Medium 15544841
2006 MCHR1 knockout mice display anxiolytic-like behavior across multiple paradigms (open field, elevated plus maze, social interaction, stress-induced hyperthermia), and show lower basal serotonin efflux in the prefrontal cortex and absent stress-induced 5-HT release compared to wild-types, linking MCHR1 signaling to serotonergic modulation of anxiety. MCHR1 knockout genetics, behavioral testing (open field, elevated plus maze, social interaction, stress-induced hyperthermia), in vivo microdialysis of 5-HT in prefrontal cortex Neuropsychopharmacology High 15988472
2006 In a neuronal-derived cell line (I3.4.2) expressing MCHR1, MCH-stimulated Ca2+ mobilization was insensitive to pertussis toxin, indicating signaling via Gαq rather than Gαi/o; cAMP assays confirmed absence of Gαi/o coupling in this neural context, suggesting the coupling profile of MCHR1 is cell-type dependent. Ca2+ mobilization assay, cAMP assay, pertussis toxin treatment, [125I]MCH saturation binding in neural-derived I3.4.2 cell line The international journal of biochemistry & cell biology Medium 16524757
2020 MCHR1 protein is abundantly localized to the primary cilium of neurons throughout the CNS (olfactory bulb, cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, midbrain, spinal cord), as demonstrated by immunohistochemistry with a validated antibody, and ciliary MCHR1 is co-expressed with diverse neurochemical markers including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and CRF. Immunohistochemistry with antibody validation; co-labeling with multiple neurochemical markers in rat and mouse brain Journal of neuroscience research Medium 32530066
2021 The ciliary transition zone protein AHI1 is required for trafficking of MCHR1 into neuronal primary cilia: Ahi1-/- neurons show significantly reduced ciliary MCHR1 without change in total or surface expression. Neurons lacking ciliary MCHR1 have significantly reduced MCH-stimulated cAMP and ERK signaling, establishing that ciliary localization of MCHR1 is necessary for its downstream signaling. Neuronal cultures from Ahi1+/+ and Ahi1-/- embryonic mice; immunofluorescence for ciliary vs total/surface MCHR1; cAMP assay; ERK activation assay after MCH stimulation The Journal of neuroscience High 33741721
2021 PDGF-BB binds directly to MCHR1 in membrane fractions of normal human dermal fibroblasts (confirmed by surface plasmon resonance), and MCHR1 mediates PDGF-BB-induced upregulation of TGFβ1 and CTGF (profibrotic factors) and modulation of intracellular cAMP; MCHR1 silencing reduced PDGF-BB signaling, identifying MCHR1 as a mediator of PDGF-BB-driven fibrotic responses. MCHR1 silencing (siRNA) in primary human dermal fibroblasts; mRNA/protein expression; surface plasmon resonance for PDGF-BB/MCHR1 binding; cAMP assay Frontiers in immunology Medium 34912333
2022 MRAP2 physically interacts with MCHR1 (demonstrated by co-immunoprecipitation and bimolecular fluorescence complementation) and inhibits MCHR1 signaling in vitro. The C-terminal domain of MRAP2 is required for pharmacological modulation of intracellular Ca2+ cascades and membrane transport of MCHR1. Co-immunoprecipitation, bimolecular fluorescence complementation assay, functional truncation analysis of MRAP2 C-terminus, intracellular Ca2+ assay Frontiers in endocrinology Medium 35311242
2012 Disruption of MCH1R in mice leads to hypothyroidism: MCH1R-KO mice have reduced circulating iodothyronines (T4, free T4, T3, rT3) with elevated TRH and TSH, and their thyroid follicles sequester more hormone and secrete less T4 upon TSH challenge or 125I loading, indicating that MCHR1 signaling regulates thyroid hormone secretion. MCH1R knockout mice, serum hormone measurements, thyroid follicle size analysis, T4/T3 content in thyroid glands, TSH challenge and 125I secretion assay Endocrinology Medium 23024261

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 419 10421367
2000 The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. The European journal of neuroscience 240 10762350
1999 Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). FEBS letters 163 10471841
1999 Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor. Biochemical and biophysical research communications 145 10441476
2007 SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast. The Journal of biological chemistry 102 17675291
2007 Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. The Journal of pharmacology and experimental therapeutics 100 17237257
2013 SLC1 glutamate transporters. Pflugers Archiv : European journal of physiology 86 24240778
2014 The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling. PLoS pathogens 84 24586162
2006 Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1) in mice exerts anxiolytic-like behavioral effects. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 82 15988472
2007 Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life sciences 62 17655875
1998 Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the gene. Biochimica et biophysica acta 61 9531978
2006 A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression. Biological psychiatry 60 16934771
2005 Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice. Regulatory peptides 58 15544841
2010 Recent updates on the melanin-concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists. Journal of molecular neuroscience : MN 55 20582487
2001 Structure-activity relationship studies of melanin-concentrating hormone (MCH)-related peptide ligands at SLC-1, the human MCH receptor. The Journal of biological chemistry 54 11278733
2010 Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats. Psychopharmacology 50 20628734
2010 Phylogenetic analysis of the vertebrate excitatory/neutral amino acid transporter (SLC1/EAAT) family reveals lineage specific subfamilies. BMC evolutionary biology 49 20429920
2016 Discovery of (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone (AZD1979), a Melanin Concentrating Hormone Receptor 1 (MCHr1) Antagonist with Favorable Physicochemical Properties. Journal of medicinal chemistry 45 26741166
2011 Topology of 1-acyl-sn-glycerol-3-phosphate acyltransferases SLC1 and ALE1 and related membrane-bound O-acyltransferases (MBOATs) of Saccharomyces cerevisiae. The Journal of biological chemistry 42 21849510
2002 Human immune cells express ppMCH mRNA and functional MCHR1 receptor. FEBS letters 41 12220661
2001 SLC-1 receptor mediates effect of melanin-concentrating hormone on feeding behavior in rat: a structure-activity study. The Journal of pharmacology and experimental therapeutics 40 11561073
2017 PPARδ promotes tumor progression via activation of Glut1 and SLC1-A5 transcription. Carcinogenesis 36 28419191
2011 Allele-specific, age-dependent and BMI-associated DNA methylation of human MCHR1. PloS one 36 21637341
2004 Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 2. Bioorganic & medicinal chemistry letters 36 15341943
2001 Endogenous melanin-concentrating hormone receptor SLC-1 in human melanoma SK-MEL-37 cells. Biochemical and biophysical research communications 33 11708774
2011 Chlamydia trachomatis Slc1 is a type III secretion chaperone that enhances the translocation of its invasion effector substrate TARP. Molecular microbiology 31 21883523
2012 Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism: reduced appetite for calories and suppression of addictive-like behaviors. Pharmacology, biochemistry, and behavior 30 22705492
2008 Enantioselective synthesis of SNAP-7941: chiral dihydropyrimidone inhibitor of MCH1-R. The Journal of organic chemistry 30 18767801
1996 Molecular and genetic characterization of SLC1, a putative Saccharomyces cerevisiae homolog of the metazoan cytoplasmic dynein light chain 1. Molecular & general genetics : MGG 30 8628245
2012 Melanin concentrating hormone receptor 1 (MCHR1) antagonists-Still a viable approach for obesity treatment? Bioorganic & medicinal chemistry letters 27 22954736
2004 Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 1. Bioorganic & medicinal chemistry letters 25 15341942
2020 Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner. Journal of neuroscience research 24 32530066
2004 Osteoporosis in MCHR1-deficient mice. Biochemical and biophysical research communications 23 15147966
2018 Melanin-Concentrating Hormone (MCH) and MCH-R1 in the Locus Coeruleus May Be Involved in the Regulation of Depressive-Like Behavior. The international journal of neuropsychopharmacology 22 30335150
2009 Changes in oil content of transgenic soybeans expressing the yeast SLC1 gene. Lipids 22 19768478
2005 Mutation analysis of the MCHR1 gene in human obesity. European journal of endocrinology 22 15941924
2021 PDGF Promotes Dermal Fibroblast Activation via a Novel Mechanism Mediated by Signaling Through MCHR1. Frontiers in immunology 21 34912333
2012 Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists. Bioorganic & medicinal chemistry letters 21 22487182
2002 Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides 21 12182940
2007 Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice. Behavioural brain research 20 17270288
2012 [¹⁸F]FE@SNAP-A new PET tracer for the melanin concentrating hormone receptor 1 (MCHR1): microfluidic and vessel-based approaches. Bioorganic & medicinal chemistry 19 22921745
2006 Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 19 16741940
2013 Fighting obesity with a sugar-based library: discovery of novel MCH-1R antagonists by a new computational-VAST approach for exploration of GPCR binding sites. Journal of chemical information and modeling 15 23590178
2012 Discovery of a novel melanin concentrating hormone receptor 1 (MCHR1) antagonist with reduced hERG inhibition. Bioorganic & medicinal chemistry letters 15 22542010
2012 Antiobesity effects of melanin-concentrating hormone receptor 1 (MCH-R1) antagonists. Handbook of experimental pharmacology 14 22249825
2012 Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: part 2. Bioorganic & medicinal chemistry letters 13 22497763
2007 Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists. Bioorganic & medicinal chemistry letters 13 17329101
2021 The Transition Zone Protein AHI1 Regulates Neuronal Ciliary Trafficking of MCHR1 and Its Downstream Signaling Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 33741721
2016 Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor. Journal of medicinal chemistry 12 27564419
2013 Preparation and First Preclinical Evaluation of [(18)F]FE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1). Scientia pharmaceutica 12 24106662
2012 Radiosynthesis of [11C]SNAP-7941--the first PET-tracer for the melanin concentrating hormone receptor 1 (MCHR1). Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 12 22858577
2006 An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists. Bioorganic & medicinal chemistry letters 12 17234405
2005 Synthesis and structure-activity relationships of biarylcarboxamide bis-aminopyrrolidine urea derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Bioorganic & medicinal chemistry letters 12 15950467
2011 Strategies to lower the Pgp efflux liability in a series of potent indole azetidine MCHR1 antagonists. Bioorganic & medicinal chemistry letters 11 21802292
2007 Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity. Bioorganic & medicinal chemistry 11 17407817
2006 4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists. Bioorganic & medicinal chemistry letters 11 16919453
2006 Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity. Bioorganic & medicinal chemistry letters 11 17350253
2012 An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors. Bioorganic & medicinal chemistry letters 10 22377519
2010 Anxiolytic effects of the MCH1R antagonist TPI 1361-17. Journal of molecular neuroscience : MN 10 20635163
2009 Optimization of piperidin-4-yl-urea-containing melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Reducing hERG-associated liabilities. Bioorganic & medicinal chemistry letters 10 19500982
2004 Identification and characterization of single-nucleotide polymorphisms in MCH-R1 and MCH-R2. Obesity research 10 15340116
2022 Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein. Frontiers in endocrinology 9 35311242
2013 Evaluation of AMG 076, a potent and selective MCHR1 antagonist, in rodent and primate obesity models. Pharmacology research & perspectives 9 25505557
2010 Discovery of novel, orally available benzimidazoles as melanin concentrating hormone receptor 1 (MCHR1) antagonists. Bioorganic & medicinal chemistry letters 9 20724156
2006 Characterization of a neuronal cell line expressing native human melanin-concentrating hormone receptor 1 (MCHR1). The international journal of biochemistry & cell biology 9 16524757
2006 Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 2. Bioorganic & medicinal chemistry letters 9 16824755
2011 Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists. Bioorganic & medicinal chemistry letters 8 21420863
2010 Building a MCHR1 homology model provides insight into the receptor-antagonist contacts that are important for the development of new anti-obesity agents. Bioorganic & medicinal chemistry 8 20932767
2009 Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition. Bioorganic & medicinal chemistry letters 8 19500979
2007 Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1-R) antagonists. Current topics in medicinal chemistry 8 17897030
2007 Single nucleotide polymorphisms of the MCHR1 gene do not affect metabolism in humans. Obesity (Silver Spring, Md.) 8 18198296
2006 Identification of substituted 4-aminopiperidines and 3-aminopyrrolidines as potent MCH-R1 antagonists for the treatment of obesity. Bioorganic & medicinal chemistry letters 8 16879961
2022 Identification and New Indication of Melanin-Concentrating Hormone Receptor 1 (MCHR1) Antagonist Derived from Machine Learning and Transcriptome-Based Drug Repositioning Approaches. International journal of molecular sciences 7 35409167
2011 Immunodetection of the MCHR1 antibody in vitiligo patient sera. International journal of molecular medicine 7 21369690
2011 4-arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1). Bioorganic & medicinal chemistry letters 7 22137790
2010 Acute homeostatic responses to increased fat consumption in MCH1R knockout mice. Journal of molecular neuroscience : MN 7 20411353
2009 Identification and characterization of a selective radioligand for melanin-concentrating hormone 1-receptor (MCH1R). Bioorganic & medicinal chemistry letters 7 19361985
2009 Identification of 2-aminobenzimidazoles as potent melanin-concentrating hormone 1-receptor (MCH1R) antagonists. Bioorganic & medicinal chemistry letters 7 19457661
2006 Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 1. Bioorganic & medicinal chemistry letters 7 16814542
2023 Saccharomyces cerevisiae Δ9-desaturase Ole1 forms a supercomplex with Slc1 and Dga1. The Journal of biological chemistry 6 37269945
2021 MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice. Molecules (Basel, Switzerland) 6 33673598
2017 Systematic Data Mining Reveals Synergistic H3R/MCHR1 Ligands. ACS medicinal chemistry letters 6 28626527
2014 Profiling the interaction mechanism of quinoline/quinazoline derivatives as MCHR1 antagonists: an in silico method. International journal of molecular sciences 6 25257526
2013 Syntheses of precursors and reference compounds of the melanin-concentrating hormone receptor 1 (MCHR1) tracers [¹¹C]SNAP-7941 and [¹⁸F]FE@SNAP for positron emission tomography. Molecules (Basel, Switzerland) 6 24084017
2008 Discovery of 1,3-disubstituted-1H-pyrrole derivatives as potent melanin-concentrating hormone receptor 1 (MCH-R1) antagonists. Bioorganic & medicinal chemistry letters 6 18682323
2007 Synthesis and structure-activity relationships of spirohydantoin-derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Bioorganic & medicinal chemistry letters 6 17350839
2022 hERG Optimization of Benzofuro-Pyridine and Pyrazino-Indole Derivatives as MCHR1 Antagonists. ChemMedChem 5 35041296
2020 PyRod Enables Rational Homology Model-based Virtual Screening Against MCHR1. Molecular informatics 5 32329245
2019 In vitro Radiopharmaceutical Evidence for MCHR1 Binding Sites in Murine Brown Adipocytes. Frontiers in endocrinology 5 31244769
2016 Evolution of physicochemical properties of melanin concentrating hormone receptor 1 (MCHr1) antagonists. Bioorganic & medicinal chemistry letters 5 27595423
2013 Synthesis and SAR study of pyrrolo[3,4-b]pyridin-7(6H)-one derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonists. Bioorganic & medicinal chemistry letters 5 23411080
2007 Melanin concentrating hormone receptor antagonists as antiobesity agents: from M2 to MCHR-1. Current topics in medicinal chemistry 5 17897031
2003 Different structural requirements for melanin-concentrating hormone (MCH) interacting with rat MCH-R1 (SLC-1) and mouse B16 cell MCH-R. Journal of receptor and signal transduction research 5 12680590
2022 Acute intrahippocampal administration of melanin-concentrating hormone impairs memory consolidation and decreases the expression of MCHR-1 and TrkB receptors. Progress in neuro-psychopharmacology & biological psychiatry 4 36565982
2016 Mechanisms for Hepatobiliary Toxicity in Rats Treated with an Antagonist of Melanin Concentrating Hormone Receptor 1 (MCHR1). Toxicological sciences : an official journal of the Society of Toxicology 4 28025230
2015 Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup. Bioorganic & medicinal chemistry letters 4 26022839
2012 Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function. Endocrinology 4 23024261
2025 The 1-acylglycerol-3-phosphate acyltransferase Slc1 is required to regulate mitochondria and lipid droplets. Microbiological research 3 39892319
2019 SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [18F]FE@SNAP and [11C]SNAP-7941. Molecular imaging and biology 3 29948643
1996 Physical mapping of a centromere-proximal region of chromosome IV-L defines the placement of genes USO1, MBP1, PSA1 and SLC1. Yeast (Chichester, England) 2 8701613

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