Cited by 179Regulation of Appetite and ObesityPharmacology and Obesity TreatmentAdipose Tissue and Metabolism

The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.

RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals

Open access

Chen, Kong Y., Muniyappa, Ranganath, Abel, Brent S., Mullins, Katherine P., Staker, Pamela, Brychta, Robert J., Zhao, Xiongce, Ring, Michael, Psota, Tricia L., Cone, Roger D., Panaro, Brandon L., Gottesdiener, Keith M., Van der Ploeg, Lex H.T., Reitman, Marc L., Skarulis, Monica C.·2015·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2014-4024PMC PMC4399297

Open this paper in CoChat — free account Open PDF

Abstract

CONTEXT: Activation of the melanocortin-4 receptor (MC4R) with the synthetic agonist RM-493 decreases body weight and increases energy expenditure (EE) in nonhuman primates. The effects of MC4R agonists on EE in humans have not been examined to date. OBJECTIVE, DESIGN, AND SETTING: In a randomized, double-blind, placebo-controlled, crossover study, we examined the effects of the MC4R agonist RM-493 on resting energy expenditure (REE) in obese subjects in an inpatient setting. STUDY PARTICIPANTS AND METHODS: Twelve healthy adults (6 men and 6 women) with body mass index of 35.7 ± 2.9 kg/m(2) (mean ± SD) received RM-493 (1 mg/24 h) or placebo by continuous subcutaneous infusion over 72 hours, followed immediately by crossover to the alternate treatment. All subjects received a weight-maintenance diet (50% carbohydrate, 30% fat, and 20% protein) and performed 30 minutes of standardized exercise daily. Continuous EE was measured on the third treatment day in a room calorimeter, and REE in the fasting state was defined as the mean of 2 30-minute resting periods. RESULTS: RM-493 increased REE vs placebo by 6.4% (95% confidence interval, 0.68-13.02%), on average by 111 kcal/24 h (95% confidence interval, 15-207 kcal, P = .03). Total daily EE trended higher, whereas the thermic effect of a test meal and exercise EE did not differ significantly. The 23-hour nonexercise respiratory quotient was lower during RM-493 treatment (0.833 ± 0.021 vs 0.848 ± 0.022, P = .02). No adverse effect on heart rate or blood pressure was observed. CONCLUSIONS: Short-term administration of the MC4R agonist RM-493 increases REE and shifts substrate oxidation to fat in obese individuals.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1210/jc.2014-4024

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

RETRACTED: Evaluation of the Safety and Efficacy of Bremelanotide, a Melanocortin Receptor Agonist, in Female Subjects with Arousal Disorder: A Double-Blind Placebo-Controlled, Fixed Dose, Randomized Study
Safarinejad, M. R. (2008) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2007.00698.x · Cited by 69
Retracted
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber.
Ravussin, E., Lillioja, S., Anderson, T. E., Christin, L., & Bogardus, C. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112749 · Cited by 1,166
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
Vaisse, C., Clement, K., Durand, E., Hercberg, S., Guy-Grand, B., & Froguel, P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9238 · Cited by 897
Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ
ZURLO, F., Lillioja, S., Puente, A. E.-D., Nyomba, B. L. G., Raz, I., Saad, M. F., Swinburn, B. A., Knowler, W. C., Bogardus, C., & Ravussin, É. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.5.e650 · Cited by 709
Studies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615
Integration of NPY, AGRP, and Melanocortin Signals in the Hypothalamic Paraventricular Nucleus
Cowley, M. A., Pronchuk, N., Fan, W., Dinulescu, D. M., Colmers, W. F., & Cone, R. D. (1999) · Neuron · doi:10.1016/s0896-6273(00)80829-6 · Cited by 612
The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology
Tao, Y.-X. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0037 · Cited by 531
Modulation of Blood Pressure by Central Melanocortinergic Pathways
Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., Cameron, G. S., Astruc, B., Mayer, J. P., Brage, S., See, T. C., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0803085 · Cited by 477
The Central Melanocortin System and Energy Homeostasis
Cone, R. D. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(99)00153-8 · Cited by 351

Show all 30 references

Sorted by citations

Items 101–179 of 179

Setmelanotide: A Melanocortin-4 Receptor Agonist for the Treatment of Severe Obesity Due to Hypothalamic Dysfunction
Qamar, S., Mallik, R., & Makaronidis, J. (2024) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2024.20.2.9 · Cited by 16
Eating disorder animal model
Treasure, J. L., & Eid, L. (2019) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000550 · Cited by 15
Structural Analysis of Setmelanotide Binding to MC4R Variants in Comparison to Wild-Type Receptor
Hammad, M. M., Mohammad, A., Alam-Eldin, N., Madhu, D., Al‐Mulla, F., Abu‐Farha, M., & Abubaker, J. A. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120857 · Cited by 12
Neurochemical Basis of Inter-Organ Crosstalk in Health and Obesity: Focus on the Hypothalamus and the Brainstem
Haspula, D., & Cui, Z. (2023) · Cells · doi:10.3390/cells12131801 · Cited by 12
Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
Salum, K. C. R., de Souza, G. O., Abreu, G. D. M., Campos, M., Kohlrausch, F. B., Carneiro, J. R. I., Neto, J. F. N., Magno, F. C. C. M., Rosado, E. L., Palhinha, L., et al. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.608840 · Cited by 11
Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases
Graves, L. E., Khouri, J. M., Kristidis, P., & Verge, C. F. (2021) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.15407 · Cited by 15
Management of Monogenic and Syndromic Obesity
Han, J. C., Rasmussen, M. C., Forte, A. R., Schrage, S. B., Zafar, S., & Haqq, A. M. (2023) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2023.08.005 · Cited by 16
Binding, Thermodynamics, and Selectivity of a Non-peptide Antagonist to the Melanocortin-4 Receptor
Saleh, N., Kleinau, G., Heyder, N., Clark, T., Hildebrand, P. W., & Scheerer, P. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00560 · Cited by 11
Do anti-obesity medical treatments have a direct effect on adipose tissue?
Vergès, B. L. (2024) · Annales d Endocrinologie · doi:10.1016/j.ando.2024.05.021 · Cited by 9
Discovery of Nanomolar Melanocortin-3 Receptor (MC3R)-Selective Small Molecule Pyrrolidine Bis-Cyclic Guanidine Agonist Compounds Via a High-Throughput “Unbiased” Screening Campaign
Doering, S. R., Freeman, K. T., Debevec, G., Geer, P., Santos, R. G., Lavoi, T. M., Giulianotti, M. A., Pinilla, C., Appel, J. R., Houghten, R. A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02041 · Cited by 9
Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions
Copperi, F., Kim, J. D., & Diano, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.725709 · Cited by 9
Targeting melanocortin 4 receptor to treat sleep-disordered breathing in mice
Amorim, M. R., Williams, N. R., Aung, O., Ruiz, M. A., Anokye‐Danso, F., de Deus, J. L., Xiong, J., Dergacheva, O., Bevans‐Fonti, S., Lee, S. M., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci177823 · Cited by 8
New Thoughts on Pediatric Genetic Obesity: Pathogenesis, Clinical Characteristics and Treatment Approach
Stagi, S., Bianconi, M., Sammarco, M. A., Artuso, R., Giglio, S., & de Martino, M. (2017) · InTech eBooks · doi:10.5772/66128 · Cited by 7
Neuroendocrine manifestations of Erdheim–Chester disease
Manaka, K., Sato, J., & Makita, N. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820683-6.00010-5 · Cited by 8
New hormone treatment for obesity caused by POMC-deficiency
Low, M. J. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.156 · Cited by 8
Incorporation of Agouti-Related Protein (AgRP) Human Single Nucleotide Polymorphisms (SNPs) in the AgRP-Derived Macrocyclic Scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe- d Pro] Decreases Melanocortin-4 Receptor Antagonist Potency and Results in the Discovery of Melanocortin-5 Receptor Antagonists
Koerperich, Z. M., Ericson, M. D., Freeman, K. T., Speth, R. C., Pogozheva, I. D., Mosberg, H. I., & Haskell‐Luevano, C. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00860 · Cited by 8
Genetic Profiles in the Obese Population
da Fonseca, A. C. P., Bozza, P. T., & Cabello, P. H. (2020) · Springer eBooks · doi:10.1007/978-3-030-53370-0_8 · Cited by 7
Effective and appropriate use of weight loss medication in pediatric obesity: a narrative review
Chung, L. Y. (2024) · Journal of Yeungnam Medical Science · doi:10.12701/jyms.2024.00353 · Cited by 7
Regulation of feeding and therapeutic application of bioactive peptides
Ueno, H., Zhang, W., & Nakazato, M. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108187 · Cited by 7
Hormone-Replacement Therapy for Melanocyte-Stimulating Hormone Deficiency
Reitman, M. L. (2016) · New England Journal of Medicine · doi:10.1056/nejme1606919 · Cited by 7
Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway
Welling, M. S., van Rossum, E. F. C., & van den Akker, E. L. T. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf004 · Cited by 6
The management of hypothalamic obesity in craniopharyngioma
Dimitri, P. (2025) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2025.102018 · Cited by 6
Human gain-of-function MC4R variants show signaling bias and protect against obesity
Lotta, L. A., Mokrosiński, J., Mendes de Oliveira, E., Li, C., Sj, S., Luan, J., Brouwers, B., Ayinampudi, V., Bowker, N., Kerrison, N. D., et al. (2020) · Yearbook of pediatric endocrinology · doi:10.1530/ey.17.11.3 · Cited by 10
Melanocortins and Their Potential for the Treatment, Prevention and Amelioration of Complications of Diabetes
Robinson, G. N., & Pickering, R. J. (2024) · Diabetology · doi:10.3390/diabetology5010006 · Cited by 6
Melanocortin-4 Receptor Deficiency Phenotype with an Interstitial 18q Deletion: A Case Report of Severe Childhood Obesity and Tall Stature
Abdullah, S., Reginold, W., Kiss, C., Harrison, K. J., & MacKenzie, J. J. (2016) · Case Reports in Pediatrics · doi:10.1155/2016/6123150 · Cited by 6
The Melanocortin Signal System of the Hypothalamus and Its Functional State in Type 2 Diabetes Mellitus and Metabolic Syndrome
Shpakov, A. O., & Derkach, K. V. (2017) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-017-0426-y · Cited by 6
Pharmaceutical approaches to weight management: behavioural mechanisms of action
Roberts, C. A., Christiansen, P., & Halford, J. C. G. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.04.017 · Cited by 6
Strategies to Counter Weight Loss-Induced Reductions in Metabolic Rate
Palmer, B. F., & Clegg, D. J. (2019) · Current Sports Medicine Reports · doi:10.1249/jsr.0000000000000610 · Cited by 6
Anorectic state of obesity medications in the United States. Are leaner times ahead?
Li, X., & Bello, N. T. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1692815 · Cited by 6
L-Cell Expression of Melanocortin-4-Receptor Is Marginal in Most of the Small Intestine in Mice and Humans and Direct Stimulation of Small Intestinal Melanocortin-4-Receptors in Mice and Rats Does Not Affect GLP-1 Secretion
Kuhre, R. E., Modvig, I. M., Jepsen, S. L., Kizilkaya, H. S., Bæch‐Laursen, C., Smith, C. A., Reimann, F. M., Gribble, F. M., ROSENKILDE, M. M., & Holst, J. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.690387 · Cited by 5
Causes of Severe Obesity: Genes to Environment
Dash, S. (2016) · Springer eBooks · doi:10.1007/978-3-319-42536-8_3 · Cited by 5
Neuropeptides, Inflammation, and Diabetic Wound Healing: Lessons from Experimental Models and Human Subjects
Tellechea, A., Pradhan‐Nabzdyk, L., LoGerfo, F. W., & Veves, A. (2018) · Contemporary diabetes · doi:10.1007/978-3-319-89869-8_8 · Cited by 6
The Natural History of Prediabetes and Cardiovascular Disease in the Pediatric Population
Accacha, S. D., Barillas, J., Gabriel, L., Srivastava, A., Gulkarov, S., Apsan, J., Leon, J. D., & Reiss, A. B. (2026) · Biomedicines · doi:10.3390/biomedicines14010198 · Cited by 4
Setmelanotide optimization through fragment-growing, molecular docking in-silico method targeting MC4 receptor
Jia, X.-P., Fan, S., Dong, W., Li, S., Zhang, Y., Ma, Y., & Wang, S. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2204385 · Cited by 4
The MC4R agonist, setmelanotide, is associated with an improvement in hypercapnic chemosensitivity and weight loss in male mice
Rivera, A., Framnes‐DeBoer, S. N., & Arble, D. M. (2024) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2024.104370 · Cited by 4
Old and new tools to study human brain physiology: Current state, future directions and implications for metabolic regulation
Farr, O. M., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153957 · Cited by 4
The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives
Prindle, C. R., Bennett, T. L., Rajewski, B. H., Kelley, K. J., Impastato, A. C., Potterfield, R., Marks, D. L., & Delev, J. Y. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1797586 · Cited by 3
A new era in childhood obesity
Martos‐Moreno, G. Á., Guijo, B., Tena‐Sempere, M., Chowen, J. A., & Argente, J. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2026.03.006 · Cited by 5
Molecular basis of obesity disorders
Kleinendorst, L., & van Haelst, M. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-809356-6.00005-8 · Cited by 3
Genetics of Obesity
Dubern, B., Clément, K., & Poitou, C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-48559-3.00014-2 · Cited by 3
Setmelanotide in obesity: a profile of its use
Kang, C. (2022) · Drugs & Therapy Perspectives · doi:10.1007/s40267-022-00929-3 · Cited by 3
Current pharmacological approaches in obesity treatment
TİRYAKİOĞLU, P., Yilmaz, H., Demir, İ., & Yilmaz, I. C. (2023) · DAHUDER Medical Journal · doi:10.56016/dahudermj.1271677 · Cited by 4
Neuroendocrine Regulation of Appetite and Body Weight
Wilkinson, M., & Imran, S. A. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108149938.005 · Cited by 4
Measuring energy expenditure in Göttingen Minipigs using indirect calorimetry: validation and methodological considerations
Bredum, S. K., Jacobsen, J. M., Cirera, S., & Christoffersen, B. Ø. (2025) · Laboratory Animal Research · doi:10.1186/s42826-024-00233-3 · Cited by 2
High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery
Howard, C. J., Abell, N. S., Osuna, B. A., Jones, E. M., Chan, L. Y., Chan, H. W.-S., Artis, D. R., Asfaha, J. B., Bloom, J. S., Cooper, A. R., et al. (2024) · eLife · doi:10.7554/elife.104725.3 · Cited by 26
From a Cone Snail Toxin to a Competitive MC4R Antagonist
Reynaud, S., Laurin, S., Ciolek, J., Barbe, P., van Baelen, A.-C., Susset, M., Blondel, F., Ghazarian, M., Boeri, J., Driessche, M. V., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00786 · Cited by 2
Tratamento farmacológico da obesidade: passado, presente e futuro.
Geloneze, B. (2019) · HU Revista · doi:10.34019/1982-8047.2018.v44.13989 · Cited by 2
Neuroendocrine Control of Energy Stores
Cone, R. D., & Elmquist, J. K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00035-6 · Cited by 2
GPCR’s and Endocrinology
Gorvin, C. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00020-7 · Cited by 2
High resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discoveryPreprint
Howard, C. J., Abell, N. S., Osuna, B. A., Jones, E. M., Chan, L. Y., Chan, H., Artis, D. R., Asfaha, J. B., Bloom, J. S., Cooper, A. R., et al. (2024) · eLife · doi:10.7554/elife.104725.1 · Cited by 2
Récepteur MC4R : actualités de la recherche dans l’obésité et potentiels développements thérapeutiques
Duquesnoy, M., Mosbah, H., Clément, K., Dubern, B., & Poitou, C. (2020) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2020.07.002 · Cited by 1
Future Perspectives in the Management of Obesity
Garcha, S. C., & Kalra, S. (2025) · Springer eBooks · doi:10.1007/978-981-96-1651-0_6 · Cited by 1
Exploratory safety investigations in normal, freely moving Göttingen Minipigs using telemetry: Pharmacological validation
Jacobsen, J. M., & Christoffersen, B. Ø. (2025) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2025.108395 · Cited by 1
Hypothalamic Obesity and Wasting Syndromes
Uwaifo, G. I. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-030-62187-2_12 · Cited by 1
Obesity and Stress: The Melanocortin Connection
Singhal, S., & Hill, J. W. (2018) · Springer eBooks · doi:10.1007/978-3-319-89506-2_11 · Cited by 1
New advances and novel approaches in obesity pharmacotherapy
Vaamonde, J. G., Frühbeck, G., & Salvador, J. (2018) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2018.08.003 · Cited by 1
Melanocortinas y su participación en el desarrollo de la obesidad
López-Alonso, V. E., Díaz‐Urbina, D., Escartín-Pérez, R. E., & Díaz, J. M. M. (2022) · Revista Mexicana de Trastornos Alimentarios/Mexican Journal of Eating Disorders · doi:10.22201/fesi.20071523e.2020.4.643 · Cited by 1
Characterizing the Mesolimbic Dopamine Reward Pathway in a Magel2-null Mouse, a Model of Prader-Willi Syndrome
Gibson, C. L. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3pv6bf98 · Cited by 1
Adjunctive Therapy, Including Pharmacotherapy
Al-Bazz, D. Y., & Wilding, J. P. H. (2022) · Wiley eBooks · doi:10.1002/9781119695257.ch21 · Cited by 1
High resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discoveryPreprint
Howard, C. J., Abell, N. S., Osuna, B. A., Jones, E. M., Chan, L. Y., Chan, H., Artis, D. R., Asfaha, J. B., Bloom, J. S., Cooper, A. R., et al. (2025) · eLife · doi:10.7554/elife.104725.2 · Cited by 1
Ansätze wider den großen Appetit
Mai, K. (2016) · Info Diabetologie · doi:10.1007/s15034-016-0839-7
Neuronal Control of Brown Fat
Kooijman, A., van den Heuvel, J. K., & Rensen, P. C. N. (2015)
Discovery of Peptide and Peptidomimetic Based Ligands Targeting the Melanocortin Receptors: A campaign in mixture-based positional scanning, chemical topology, and structure-activity relationships
Doering, S. R. (2016) · University of Minnesota Digital Conservancy (University of Minnesota)
Osteoporosis associated with eating disorders
Robinson, L., & Misra, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00044-7
Pharmacotherapy in Pediatric Obesity: Current Status and Future Prospects
Karachaliou, F. (2020) · Interventions in Obesity & Diabetes · doi:10.31031/iod.2020.04.000582
Management of severe pediatric obesity
Chung, L. Y., & Rhie, Y. (2021) · Journal of Korean Medical Association · doi:10.5124/jkma.2021.64.6.416
Setmelanotide – from genes to targeted therapy in some rare forms of obesity
Frączkowski, D. (2021) · Farmacja Polska · doi:10.32383/farmpol/141552
Faculty Opinions recommendation of Late onset obesity in mice with targeted deletion of potassium inward rectifier Kir7.1 from cells expressing the melanocortin-4 receptor.
Daniels, D., & Mietlicki‐Baase, E. G. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734699055.793554621
Faculty Opinions recommendation of Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.
Flannick, J. A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735570136.793563021
Faculty Opinions recommendation of Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.
Shukla, A. K. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735570136.793559182
Neuropeptides, Inflammation, and Diabetic Wound Healing: Lessons from Experimental Models and Human Subjects
Mota, L., LoGerfo, F. W., Veves, A., & Pradhan‐Nabzdyk, L. (2024) · Contemporary diabetes · doi:10.1007/978-3-031-55715-6_9
Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide
Choo, Y. N., Narayanan, R., & Subramaniyan, V. (2025) · Vascular Pharmacology · doi:10.1016/j.vph.2025.107553 · Cited by 1
Review of medicines approved by the Food and Drug Administration from 2012 to 2024
Kurkin, D. V., Osadchenko, N. A., Bakulin, D. A., Morkovin, E. I., Voskresenskiy, S. A., Maltsev, D. V., Maltseva, M. O., Gorbunova, Y. V., Marincheva, O. V., Zvereva, V. I., et al. (2025) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2025-13-6-432-486
BindingDB Entry 50014427: Discovery of Nanomolar Melanocortin-3 Receptor (MC3R)-Selective Small Molecule Pyrrolidine Bis-Cyclic Guanidine Agonist Compounds Via a High-Throughput "Unbiased" Screening Campaign.
BindingDB (2022) · UC San Diego · doi:10.7270/q2gt5s0n
BindingDB Entry 50000909: Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1.
BindingDB (2020) · UC San Diego · doi:10.7270/q2736tcz
BindingDB Entry 50015829: Late-Stage Functionalization with Cysteine Staples Generates Potent and Selective Melanocortin Receptor-1 Agonists.
BindingDB (2023) · UC San Diego · doi:10.7270/q20c50r5
BindingDB Entry 50007962: Incorporation of Agouti-Related Protein (AgRP) Human Single Nucleotide Polymorphisms (SNPs) in the AgRP-Derived Macrocyclic Scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] Decreases Melanocortin-4 Receptor Antagonist Potency and Results in the Discovery of Melanocortin-5 Receptor Antagonists.
BindingDB (2021) · UC San Diego · doi:10.7270/q25142kg
BindingDB Entry 50016180: From a Cone Snail Toxin to a Competitive MC4R Antagonist.
BindingDB (2023) · UC San Diego · doi:10.7270/q2pv6qbw
BindingDB Entry 50000972: Discovery of Mixed Pharmacology Melanocortin-3 Agonists and Melanocortin-4 Receptor Tetrapeptide Antagonist Compounds (TACOs) Based on the Sequence Ac-Xaa
BindingDB (2020) · UC San Diego · doi:10.7270/q24170j1

Authors: Chen, K. Y., Muniyappa, R., Abel, B. S., Mullins, K. P., Staker, P., Brychta, R. J., Zhao, X., Ring, M., Psota, T. L., Cone, R. D., Panaro, B. L., Gottesdiener, K. M., Van der Ploeg, L. H. T., Reitman, M. L., & Skarulis, M. C.
Affiliations: National Institutes of Health (US)
Vanderbilt University (US)
Rhythm (United states) (US)
Rhythm Pharmaceuticals (K.M.G., L.H.T.V.d.P.), Boston, Massachusetts 02116
Corresponding author: Skarulis, Monica C.
ORCID: Chen, Kong Y.
Muniyappa, Ranganath
Abel, Brent S.
Brychta, Robert J.
Psota, Tricia L.
Cone, Roger D.
Panaro, Brandon L.
Gottesdiener, Keith M.
Reitman, Marc L.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2015-04-01
Volume: 100
Issue: 4
Pages: 1639-1645
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2014-4024
PMC: PMC4399297
OpenAlex: W2079643489
Cited by: 174
References: 30
Citations by year: 2026: 4 · 2025: 13 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 21 · 2020: 22 · 2019: 21 · 2018: 21 · 2017: 16 · 2016: 18 · 2015: 6
FWCI: 11.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (MD 20892)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070332, P30DK058404)
NIH Clinical Center
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: melanocortin-4 receptor agonist, resting energy expenditure, obesity, energy expenditure, substrate oxidation, respiratory quotient, weight loss, continuous subcutaneous infusion, thermogenesis
MeSH terms: Adult, alpha-MSH, Combined Modality Therapy, Double-Blind Method, Energy Metabolism, Female, Humans, Male, Middle Aged, Obesity, Rest, Cross-Over Studies, Anti-Obesity Agents, Receptor, Melanocortin, Type 4, Young Adult, Weight Reduction Programs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks