Affinage

MCHR1

Melanin-concentrating hormone receptor 1 · UniProt Q99705

Length
353 aa
Mass
38.9 kDa
Annotated
2026-04-28
100 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCHR1 (SLC-1/GPR24) is a G-protein-coupled receptor for melanin-concentrating hormone (MCH) that integrates energy balance, locomotion, anxiety, memory, bone homeostasis, and thyroid function through cell-type-dependent coupling to Gi/o and Gq signaling cascades. MCHR1 binds MCH with sub-nanomolar affinity and, depending on cellular context, inhibits cAMP accumulation via pertussis toxin-sensitive Gi/o proteins, mobilizes intracellular Ca²⁺ via Gq, and activates p42/p44 MAPK; in neuronal cells expressing endogenous receptor, signaling can be exclusively Gq-mediated (PMID:10421367, PMID:11708774, PMID:16524757). In the CNS, MCHR1 localizes predominantly to neuronal primary cilia, and AHI1-dependent ciliary trafficking is required for downstream cAMP and ERK signaling, establishing the cilium as a critical signaling platform for this receptor (PMID:32530066, PMID:33741721). MCHR1 is modulated by the accessory protein MRAP2, whose C-terminus inhibits MCHR1-mediated Ca²⁺ signaling and membrane transport, and can also be engaged by the non-canonical ligand PDGF-BB to drive profibrotic gene expression in dermal fibroblasts (PMID:35311242, PMID:34912333).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 High

    Identification of MCH as the endogenous ligand of the orphan receptor SLC-1 resolved the receptor's pharmacological identity and established its dual Gi/o–Gq coupling, providing the molecular basis for all subsequent MCH signaling studies.

    Evidence Radioligand binding, Ca²⁺ mobilization, cAMP inhibition in HEK293/CHO cells; GIRK and Cl⁻ current recording in Xenopus oocytes

    PMID:10421367 PMID:10441476 PMID:10471841

    Open questions at the time
    • G-protein coupling selectivity in native tissues not yet addressed
    • No structural basis for sub-nanomolar MCH binding
  2. 2001 High

    Structure-activity analysis of MCH analogs defined the minimal active peptide core (residues 6–17), essential contact residues, and the requirement for the disulfide bridge, while correlating in vitro potency with in vivo feeding responses—linking receptor pharmacology to the orexigenic phenotype.

    Evidence 57 synthetic MCH analogs tested by cAMP and GTPγS assays in HEK293 cells; ICV injection of analogs with food intake measurement in rats

    PMID:11278733 PMID:11561073

    Open questions at the time
    • No receptor mutagenesis to identify contact residues on the MCHR1 side
    • Downstream intracellular pathways mediating feeding behavior undefined
  3. 2001 High

    Demonstration that cell-type context dictates MCHR1's G-protein selectivity—exclusive Gi/o coupling in melanoma cells versus Gq-dominant coupling in neuronal cells—established that MCHR1 signaling output is not fixed but depends on the cellular G-protein repertoire.

    Evidence cAMP, Ca²⁺, and MAPK assays with pertussis toxin in SK-MEL-37 melanoma cells and IMR32-derived neuroblastoma cells expressing endogenous MCHR1

    PMID:11708774 PMID:16524757

    Open questions at the time
    • Mechanism determining G-protein selectivity (e.g., receptor phosphorylation state, scaffold proteins) unknown
    • In vivo relevance of cell-type-dependent coupling not established
  4. 2004 Medium

    MCHR1 knockout mice revealed an unexpected requirement for MCH/MCHR1 signaling in bone homeostasis, demonstrating that MCHR1 tonically stimulates bone mass and that its loss leads to osteoporosis with increased bone resorption.

    Evidence MCHR1 KO mouse bone densitometry and serum c-telopeptide measurement

    PMID:15147966

    Open questions at the time
    • Whether MCHR1 acts directly on osteoblasts/osteoclasts or indirectly via CNS pathways is unknown
    • No rescue experiment performed
  5. 2005 Medium

    Behavioral phenotyping of MCHR1-null and PMCH-null mice established that endogenous MCH–MCHR1 signaling tonically suppresses locomotor activity and promotes anxiety-like behavior, with serotonergic transmission as a downstream mediator of the anxiolytic phenotype.

    Evidence Voluntary wheel running in two independent KO lines; behavioral battery (open field, EPM, social interaction, SIH) plus in vivo microdialysis for 5-HT in prefrontal cortex of MCHR1 KO mice

    PMID:15544841 PMID:15988472

    Open questions at the time
    • Neuronal subpopulations mediating the locomotor versus anxiety phenotypes not identified
    • Circuit-level mechanism linking MCHR1 to serotonergic neuron firing not resolved
  6. 2012 Medium

    Discovery of MCHR1 expression in thyroid follicular cells and the hypothyroid phenotype of MCHR1 KO mice extended the receptor's physiological roles beyond the CNS, demonstrating a direct requirement for MCHR1 in thyroid hormone secretion.

    Evidence RT-PCR for thyroid MCHR1; KO mouse serum hormone levels; TSH challenge and ¹²⁵I secretion assay

    PMID:23024261

    Open questions at the time
    • Intracellular signaling pathway in thyroid cells (Gi vs Gq) not characterized
    • Whether MCH is delivered to thyroid via circulation or local production is unknown
  7. 2020 Medium

    Comprehensive mapping of MCHR1 to neuronal primary cilia across the CNS reframed the receptor's signaling mode, suggesting volume transmission rather than synaptic signaling as its predominant activation mechanism in the brain.

    Evidence Immunohistochemistry with validated antibody and neurochemical marker co-localization across rat and mouse brain regions

    PMID:32530066

    Open questions at the time
    • Functional consequence of ciliary versus non-ciliary MCHR1 signaling not yet distinguished in vivo
    • Source and diffusion dynamics of MCH reaching cilia not characterized
  8. 2021 High

    Demonstrating that AHI1 is required for MCHR1 ciliary trafficking and that loss of ciliary MCHR1 attenuates cAMP and ERK signaling established the primary cilium as a necessary signaling platform for MCHR1, connecting ciliopathy biology to MCH signaling.

    Evidence Ahi1 KO neuronal cultures; immunofluorescence for ciliary MCHR1; cAMP and ERK phosphorylation assays after MCH stimulation

    PMID:33741721

    Open questions at the time
    • Whether AHI1 loss phenocopies MCHR1 KO behavioral phenotypes in vivo not tested
    • Additional ciliary trafficking machinery for MCHR1 beyond AHI1 not identified
  9. 2021 Medium

    Identification of PDGF-BB as a non-canonical MCHR1 ligand that drives profibrotic signaling expanded the receptor's functional repertoire beyond neuropeptide signaling into tissue fibrosis.

    Evidence SPR binding, co-IP in dermal fibroblast membranes, MCHR1 siRNA knockdown with TGFβ1/CTGF readouts

    PMID:34912333

    Open questions at the time
    • PDGF-BB binding site on MCHR1 relative to MCH binding site not mapped
    • Independent replication of PDGF-BB as a direct MCHR1 ligand not yet reported
    • In vivo relevance of PDGF-BB–MCHR1 interaction in fibrotic disease not established
  10. 2022 Medium

    Discovery that MRAP2 physically interacts with MCHR1 and inhibits its Ca²⁺ signaling via its C-terminal domain identified the first accessory protein that modulates MCHR1 pharmacology, and intrahippocampal MCHR1 activation was shown to impair memory consolidation through TrkB downregulation.

    Evidence Co-IP and BiFC for MRAP2–MCHR1 interaction with domain truncations; intrahippocampal MCH microinjection with antagonist rescue and Western blot in rats

    PMID:35311242 PMID:36565982

    Open questions at the time
    • Stoichiometry and structural basis of MRAP2–MCHR1 complex unknown
    • Mechanism linking MCHR1 activation to TrkB downregulation not elucidated
    • Whether MRAP2 modulation occurs in vivo in neurons not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for MCH and PDGF-BB binding to MCHR1, the in vivo contribution of ciliary versus non-ciliary receptor pools to distinct physiological functions, and the cell-intrinsic determinants of G-protein coupling selectivity.
  • No high-resolution structure of MCHR1 bound to MCH or any ligand
  • In vivo cell-type-specific conditional knockout studies are lacking
  • Determinants of Gi vs Gq selectivity in native neurons remain uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005929 cilium 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3
Partners
AHI1MCHMRAP2PDGF-BB

Evidence

Reading pass · 19 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); expressed in HEK293 cells, it binds MCH with sub-nanomolar affinity and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cAMP levels, demonstrating coupling to both Gq and Gi pathways. Radioligand binding, Ca2+ mobilization assay, cAMP accumulation assay in HEK293 cells expressing recombinant SLC-1 Nature High 10421367
1999 SLC-1 (MCHR1) expressed in Xenopus oocytes couples to both Gi (activating GIRK currents) and Gq (activating phospholipase C-dependent Ca2+-dependent Cl- currents) signaling pathways upon MCH stimulation. Xenopus oocyte expression system with GIRK co-expression; electrophysiological recording of GIRK and Ca2+-dependent Cl- currents FEBS letters High 10471841
1999 MCH was isolated and identified as the endogenous ligand of the rat and human SLC-1 (MCHR1) receptor, with an EC50 of ~0.2 nM for inhibition of forskolin-stimulated cAMP accumulation in CHO cells expressing SLC-1. Brain extract purification by HPLC, cAMP inhibition assay in CHO cells stably expressing rat and human SLC-1 Biochemical and biophysical research communications High 10441476
2001 Structure-activity relationship studies defined MCH-(6-17) as the minimal sequence for full agonistic activity at MCHR1, with Met8, Arg11, and Tyr13 as essential residues; disruption of the disulfide bridge abolished agonistic activity and converted ligands to weak antagonists. cAMP inhibition assay and [35S]-GTPγS binding assay on HEK293 cells stably expressing human MCHR1, using 57 synthetic MCH analogues The Journal of biological chemistry High 11278733
2001 The rat SLC-1 (MCHR1) receptor pharmacology closely parallels that of the human receptor, and agonist potency in the cAMP inhibition assay correlates strongly with binding affinity and in vivo feeding effects after ICV injection, establishing SLC-1 as the receptor mediating MCH-induced feeding behavior. cAMP inhibition assay and [125I]S36057 radioligand binding on rat recombinant SLC-1; ICV injection of MCH analogs with food intake measurement in rats The Journal of pharmacology and experimental therapeutics High 11561073
2001 In SK-MEL-37 human melanoma cells expressing endogenous SLC-1 (MCHR1), MCH inhibits cAMP accumulation and activates p42/p44 MAPK in a pertussis toxin-sensitive manner, indicating exclusive coupling to Gαi/Gαo in this cell context; Gαq-mediated Ca2+ mobilization was absent, showing cell-type-dependent G-protein selectivity. cAMP accumulation assay, MAPK activation assay, pertussis toxin treatment, Ca2+ measurement in SK-MEL-37 cells and CHO/293 cells overexpressing SLC-1 Biochemical and biophysical research communications High 11708774
2002 Human immune cells (PBMCs) express functional MCHR1 that couples to both cAMP synthesis and calcium mobilization upon MCH stimulation; MCH treatment decreases CD3-stimulated PBMC proliferation in vitro, indicating an immunomodulatory role for MCH/MCHR1 signaling. RT-PCR, FACS, in vitro cAMP and Ca2+ assays, cell proliferation assay in human PBMCs 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 coupling, while MCH-R2 utilizes exclusively the Gq signaling pathway. Radioligand binding assay, intracellular signaling characterization (cAMP and Ca2+) in cells expressing cloned monkey receptors Peptides Medium 12182940
2004 A G34R coding SNP in MCHR1 present at 15% minor allele frequency in African-Americans does not alter receptor binding affinity or functional signaling (cAMP, Ca2+, MAPK) compared to wild-type MCHR1. Receptor binding assay, cAMP inhibition, Ca2+ mobilization, and MAPK activation assays in CHO cells expressing SNP-containing MCHR1 constructs Obesity research Medium 15340116
2004 Mice with genetic inactivation of MCHR1 (Mch1r-/-) develop osteoporosis with reduced cortical bone mass and increased serum c-telopeptide (marker of bone resorption), indicating that MCHR1 signaling is required for tonic stimulation of bone mass. MCHR1 knockout mouse generation, bone densitometry, serum c-telopeptide measurement Biochemical and biophysical research communications Medium 15147966
2005 Mch1r-/- mice show significantly enhanced voluntary wheel running activity, and Pmch-/- mice show similar enhancement, demonstrating that endogenous MCH signaling through MCH1R plays an inhibitory role in regulating locomotor activity; naloxone suppresses wheel running in both genotypes, implicating opioid regulation downstream. Voluntary wheel running measurement in Mch1r-/- and Pmch-/- knockout mice; naloxone pharmacological challenge; dynorphin mRNA measurement Regulatory peptides Medium 15544841
2006 MCHR1 null mutant mice display anxiolytic-like behavior across multiple behavioral paradigms (open field, elevated plus maze, social interaction, stress-induced hyperthermia); baseline serotonin levels in the prefrontal cortex are lower in MCHR1 KO mice, and forced swim-induced 5-HT efflux is absent, placing MCHR1 upstream of serotonergic transmission in modulating anxiety. MCHR1 knockout mouse behavioral testing (open field, EPM, social interaction, SIH), in vivo microdialysis for serotonin measurement in prefrontal cortex Neuropsychopharmacology Medium 15988472
2006 A neuroblastoma-derived cell line (I3.4.2) with high endogenous MCHR1 expression shows MCH-stimulated Ca2+ mobilization that is insensitive to pertussis toxin and absent cAMP signaling, indicating that in neural-derived cells MCHR1 signals preferentially through Gαq rather than Gαi/o. Pertussis toxin treatment, Ca2+ mobilization assay, cAMP accumulation assay in IMR32-derived neuronal cell line expressing native MCHR1 The international journal of biochemistry & cell biology Medium 16524757
2020 MCHR1 protein localizes abundantly to primary cilia on neurons throughout the murine CNS, as determined by immunohistochemistry with a validated specific antibody; ciliary MCHR1 co-localizes with diverse neurochemical markers (TH, calretinin, kisspeptin, estrogen receptor, OT, AVP, CRF), suggesting non-synaptic volume transmission as a predominant mode of MCH signaling. Immunohistochemistry with specificity-validated antibody, multiple neurochemical marker co-localization in rat and mouse CNS 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 reduced ciliary MCHR1 with normal total and surface expression, and have significantly decreased cAMP and ERK signaling downstream of MCH stimulation, demonstrating that ciliary localization of MCHR1 is necessary for its signaling. Neuronal cultures from Ahi1+/+ and Ahi1-/- embryonic mice, immunofluorescence for ciliary MCHR1, cAMP assay, ERK phosphorylation assay after MCH stimulation The Journal of neuroscience High 33741721
2021 PDGF-BB directly binds MCHR1 in membrane fractions of normal human dermal fibroblasts (confirmed by surface plasmon resonance), upregulates MCHR1 expression, and signals through MCHR1 to modulate intracellular cAMP and induce TGFβ1 and CTGF expression; MCHR1 silencing blocks these profibrotic responses. Co-IP/membrane fraction binding, surface plasmon resonance, MCHR1 siRNA knockdown, cAMP assay, TGFβ1/CTGF mRNA and protein measurement in normal human dermal fibroblasts Frontiers in immunology Medium 34912333
2022 MRAP2 interacts with MCHR1 (confirmed by co-immunoprecipitation and bimolecular fluorescence complementation) and inhibits MCHR1-mediated intracellular Ca2+ signaling; the C-terminal domain of MRAP2 is required for this pharmacological modulation and for effects on MCHR1 membrane transport. Co-immunoprecipitation, bimolecular fluorescence complementation, Ca2+ signaling assay with MRAP2 truncation constructs Frontiers in endocrinology Medium 35311242
2012 MCHR1 mRNA is expressed in thyroid follicular cells; MCH1R-knockout mice exhibit reduced circulating thyroid hormones (T4, fT4, T3, rT3) with elevated TRH and TSH, and upon TSH challenge their thyroids secrete lower amounts of T4, demonstrating that MCHR1 signaling is required for normal thyroid hormone secretion. RT-PCR for thyroid MCHR1 expression, MCH1R knockout mouse phenotyping (serum hormone measurements), TSH challenge experiment, 125I secretion assay Endocrinology Medium 23024261
2022 Intrahippocampal MCH administration impairs memory consolidation and decreases hippocampal MCHR1 and TrkB receptor expression without altering BDNF or NMDA receptor subunit levels; co-administration with MCHR1 antagonist ATC-0175 reverses memory impairment, placing MCHR1 activation upstream of TrkB downregulation in hippocampal memory consolidation. Bilateral intrahippocampal MCH microinjection in rats, novel object recognition test, elevated plus maze, Western blot/qPCR for MCHR1, TrkB, BDNF, NR1, NR2A, NR2B; pharmacological rescue with MCHR1 antagonist Progress in neuro-psychopharmacology & biological psychiatry Medium 36565982

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 418 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 85 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 83 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 81 15988472
2007 Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life sciences 61 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 59 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 Phylogenetic analysis of the vertebrate excitatory/neutral amino acid transporter (SLC1/EAAT) family reveals lineage specific subfamilies. BMC evolutionary biology 49 20429920
2010 Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats. Psychopharmacology 48 20628734
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 23 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
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
2021 PDGF Promotes Dermal Fibroblast Activation via a Novel Mechanism Mediated by Signaling Through MCHR1. Frontiers in immunology 18 34912333
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
2000 Utility of the Arabidopsis FAE1 and yeast SLC1-1 genes for improvements in erucic acid and oil content in rapeseed. Biochemical Society transactions 15 11171262
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
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
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 3 36565982
2019 SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [18F]FE@SNAP and [11C]SNAP-7941. Molecular imaging and biology 3 29948643