Cat. No.: HY-19870

Setmelanotide

(Synonyms: RM-493; BIM-22493; IRC-022493)

8 Cited Publications

Customer Review

Based on 8 publication(s) in Google Scholar

Setmelanotide (RM-493) is a blood-brain barrier-permeable, selective MC4R agonist with a K_i value of 2.1 nM for hMC4R. Setmelanotide activates the CaMKK2/AMPK signaling pathway. Setmelanotide mediates body weight homeostasis, feeding regulation and energy expenditure modulation; it reduces food intake, induces weight loss, decreases obesity severity, increases daytime activity and energy expenditure, lowers levels of leptin, triglycerides, fasting insulin and diastolic blood pressure, improves insulin sensitivity, glucose tolerance and fatty liver condition, and reverses respiratory depression. Setmelanotide is applicable to research related to obesity, hyperinsulinemia, fatty liver and respiratory depression.

For research use only. We do not sell to patients.

Purity: 99.99%
CAS No.: 920014-72-8
Formula: C₄₉H₆₈N₁₈O₉S₂
Molecular Weight:1117.31

Storage:

Sealed storage, away from moisture.

Powder -80°C, 2 years , -20°C, 1 year

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Setmelanotide Chemical Structure

CAS No.: 920014-72-8

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (8)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

MC4R

2.1 nM (Ki)

MC1R

3.9 nM (Ki)

MC3R

10 nM (Ki)

MC5R

430 nM (Ki)

All Melanocortin Receptor Isoforms :

All Calmodulin Isoforms :

All AMPK Isoforms :

In Vitro

Setmelanotide binds to hMC1R, MC3R, MC4R and rat MC4R with high affinity, while it shows weak binding affinity to hMC5R^[1].
Setmelanotide (increasing concentrations; treated at 37°C for 40 min) acts as an agonist to stimulate cAMP production in CHO-K1 cells expressing hMC1R, hMC3R, hMC4R, and rat MC4R; it shows weak activity on hMC5R and no activity on mouse MC2R^[1].
Setmelanotide is a potent agonist of hMC4R, with a binding K_i of 2.1 nM and a cAMP EC₅₀ of 0.27 nM in CHO-K1 cells, and exhibits low potency against hMC1R, hMC3R and hMC5R^[4].
Setmelanotide (>1.0×10⁻⁶ M) has no affinity for the μ-opioid receptor, as its IC₅₀ exceeds 1.0×10⁻⁶ M in competitive radioligand binding assays^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Setmelanotide (300 nmol/kg/day; subcutaneous injection; continuous administration for 14 days) induces weight loss, improves hyperinsulinemia, reduces total cholesterol and leptin levels, and reverses hepatic steatosis in diet-induced obese C57BL/6J mice^[1].
Monoacetate of Setmelanotide (6.4 μmol; intraperitoneal injection; single dose) acutely improves glucose clearance in leptin-deficient obese and glucose-intolerant C57BL/6J mice^[1].
Monoacetate of Setmelanotide (6.4 μmol; intraperitoneal injection; single dose) suppresses refeeding-induced food intake in C57BL/6J mice fed a normal diet, and this effect depends on functional MC4R rather than MC3R^[1].
Monoacetate of Setmelanotide (0.17-0.5 mg/kg/day; administered via a 2-week minipump every two weeks; for 8 weeks or variable duration) reduces peak body weight by 13.5% in diet-induced obese rhesus monkeys, improves insulin sensitivity and cardiovascular function, and does not cause adverse increases in heart rate or blood pressure; whereas lower doses only improve insulin sensitivity with minimal effects on body weight or cardiovascular parameters^[2].
Monoacetate of Setmelanotide (0.05 mg/kg; i.p.; single administration) activates PVN MC4R neurons via the CaMKK2/AMPK signaling pathway, thereby normalizing food intake during short-term refeeding in rats with hypothalamic obesity^[3].
Setmelanotide (0.05 mg/kg; i.p.; once daily) activates PVN MC4R neurons via the CaMKK2/AMPK signaling pathway, reduces food intake, body weight, Lee index and perirenal adipose tissue weight, thereby reversing hypothalamic obesity in rats^[3].
Monoacetate of Setmelanotide (6.4 µmole-1.34 mg/kg/day; intraperitoneal injection, subcutaneous injection; single injection, daily administration; for 14 consecutive days) induces MC4R-dependent feeding suppression and body weight loss in diet-induced obese mice^[4].
Monoacetate of Setmelanotide (100-500 nmol/kg; subcutaneous injection; single administration) suppresses food intake in fasted male Sprague-Dawley rats^[4].
Monoacetate of Setmelanotide (1 mg/kg; i.p.; single administration) effectively treats morphine-induced opioid-induced respiratory depression (OIRD) in lean male C57BL/6J mice by increasing respiratory rate and reducing apnea index, without impairing opioid analgesic effects^[5].
Monoacetate of Setmelanotide (1 mg/kg; i.p.; single administration) effectively treats morphine-induced opioid-related respiratory depression in obese male C57BL/6J mice by increasing respiratory rate and reducing the frequency and duration of apnea, without affecting opioid analgesic effects^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6J (male, 10 months old, diet-induced obese)^[1]
Dosage:

300 nmol/kg/day
Administration:

s.c.; continuous; 14 days
Result:

Reduced food intake to ~50% of controls on day 1, increasing to 75% of control levels by day 4, with no significant difference by day 12.
Lowered fasting serum insulin, glucose, and HOMA-IR values significantly.
Reduced serum leptin and total cholesterol levels significantly.
Improved liver steatosis significantly (P < 0.05).
Increased liver-specific Cpt1a expression modestly but significantly.

Animal Model:

C57BL/6J (male, 10 months old, leptin-deficient)^[1]
Dosage:

6.4 μmol
Administration:

i.p.; single injection
Result:

Improved glucose clearance significantly compared to saline-treated controls.

Animal Model:

C57BL/6J (female, 10 months old; wild-type, MC3R knockout, MC4R knockout littermates)^[1]
Dosage:

6.4 μmol
Administration:

i.p.; single injection
Result:

Inhibited refeeding-induced food intake in WT and MC3RKO mice.
Showed no inhibitory effect on refeeding-induced food intake in MC4RKO mice.

Animal Model:

mature adult male (age 9-11 years, body weight 9-19 kg; 9 diet-sensitive/obese, insulin-resistant, hypertensive; 3 diet-resistant/lean, normotensive)^[2]
Dosage:

0.5 mg/kg/day (8-week treatment); 0.17 mg/kg/day (subsequent treatment period)
Administration:

s.c.; via biweekly 2-week minipumps; 8 weeks (0.5 mg/kg/day); variable duration (0.17 mg/kg/day)
Result:

Decreased food intake by 35% in the first week, normalized by weeks 4-7, and increased during week 8.
Reached peak weight loss of 13.5% of total body weight (average 1.5 kg lost over 8 weeks), with weight loss persisting for 2 weeks post-treatment before recovery began.
Nearly doubled daytime activity by treatment end (P = 0.037, repeated-measures ANOVA).
Increased energy expenditure (CO₂ production) by 14% (P = 0.0134, paired t-test) compared to baseline.
Decreased core body temperature by ~0.5°C (P = 0.0161, repeated-measures ANOVA).
Reduced fat mass by 18.8% (1.04 kg) in diet-sensitive animals and 38.3% (0.75 kg) in diet-resistant animals; fat mass remained significantly reduced in diet-sensitive animals post-washout.
Decreased lean mass by 4.9% in diet-sensitive animals.
Decreased fasting leptin levels significantly in diet-sensitive animals (P < 0.001), with the magnitude of leptin decrease correlating with weight loss (r² = 0.6634, P = 0.0023).
Reduced fasting serum triglyceride levels significantly at 8 weeks (P = 0.0238, ANOVA).
Improved fasting insulin levels and homeostasis model assessment insulin resistance significantly in diet-sensitive animals, with reduced insulin secretion (area under the curve) and improved glucose clearance (area under the curve) during intravenous glucose tolerance testing; these improvements persisted for 4 weeks post-treatment.
Decreased heart rate significantly overall (P = 0.008, repeated-measures ANOVA), with a 13-bpm reduction in diet-sensitive animals, and reduced diastolic blood pressure significantly (P = 0.02, repeated-measures ANOVA); systolic blood pressure was unchanged.
No acute increases in heart rate or blood pressure were observed.
Improved insulin sensitivity with smaller effects on food intake and body weight at 0.17 mg/kg/day.
No changes to blood pressure or heart rate were observed at 0.17 mg/kg/day.

Animal Model:

Sprague-Dawley (male)^[4]
Dosage:

100 nmol/kg; 500 nmol/kg
Administration:

s.c.; single injection
Result:

Reduced food intake during refeeding after an overnight fast at both 100 nmol/kg and 500 nmol/kg doses.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 920014-72-8
Appearance Solid
Molecular Weight 1117.31
Formula C₄₉H₆₈N₁₈O₉S₂
Color White to off-white
Synonyms

RM-493; BIM-22493; IRC-022493
Sequence

Ac-Arg-Cys-{d-Ala}-His-{d-Phe}-Arg-Trp-Cys-NH2 (Disulfide bridge:Cys2-Cys8)
Sequence Shortening

Ac-RC-{d-Ala}-H-{d-Phe}-RWC-NH2 (Disulfide bridge:Cys2-Cys8)
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Sealed storage, away from moisture

Powder	-80°C	2 years
	-20°C	1 year

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Publications (8)

All In Vivo Efficacy StudyBio/Physico-chemical Assay

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Journal Impact Factor

Sci Transl Med

Orthopedia regulates melanocortin 4 receptor transcription and energy homeostasis. [Abstract]

2025 Jan 15;17(781):eadr6459. PMID: 39813316

Setmelanotide purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Jan 15;17(781):eadr6459. [Abstract]

Setmelanotide (2 mg/kg; i.p.; once daily for 9 d) reduced body weights and food intake and improved glucose tolerance of HFD-fed OtpQ153R/+ mice, which quickly regained body weight after the treatment was discontinued.
J Exp Med

The atypical antipsychotic risperidone targets hypothalamic melanocortin 4 receptors to cause weight gain. [Abstract]

2021 Jul 5;218(7):e20202484. PMID: 33978701

Setmelanotide purchased from MedChemExpress. Usage Cited in: J Exp Med. 2021 Jul 5;218(7):e20202484. [Abstract]

Setmelanotide (100 nM) blocked the risperidone-induced hyperpolarization of MC4R^PVH neurons.

Setmelanotide purchased from MedChemExpress. Usage Cited in: J Exp Med. 2021 Jul 5;218(7):e20202484. [Abstract]

A single dose of Setmelanotide (SET) (2 mg/kg; i.p.) suppressed fast-induced refeeding in Mc4r^fl/fl mice.

Setmelanotide purchased from MedChemExpress. Usage Cited in: J Exp Med. 2021 Jul 5;218(7):e20202484. [Abstract]

Infusion of Setmelanotide (SET) (2 mg/kg; once daily for 14 d) attenuated hyperphagia in C57BL/6 mice fed with risperidone.

Setmelanotide purchased from MedChemExpress. Usage Cited in: J Exp Med. 2021 Jul 5;218(7):e20202484. [Abstract]

Setmelanotide (SET) (2 mg/kg; once daily for 14 d) caused accelerated glucose clearance of C57BL/6 mice fed with risperidone in a GTT.
Cell Rep

Melanocortin-4 receptors activate sympathetic preganglionic neurons and elevate blood pressure via TRPV1. [Abstract]

2022 Nov 1;41(5):111579. PMID: 36323255
J Med Chem

Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists. [Abstract]

2017 Nov 9;60(21):8716-8730. PMID: 28972753
Front Immunol

Setmelanotide, a Novel, Selective Melanocortin Receptor-4 Agonist Exerts Anti-inflammatory Actions in Astrocytes and Promotes an Anti-inflammatory Macrophage Phenotype. [Abstract]

2019 Oct 4:10:2312. PMID: 31636637
Mol Metab

Lead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice. [Abstract]

2024 Nov:89:102027. PMID: 39265725
J Clin Endocrinol Metab

MC4R variants modulate α-MSH and setmelanotide induced cellular signaling at multiple levels. [Abstract]

2024 Sep 16;109(10):2452-2466. PMID: 38567654
Charles University

2019 Jun.

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (89.50 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 58.33 mg/mL (52.21 mM; Need ultrasonic)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

0.8950 mL

4.4750 mL

8.9501 mL

5 mM

0.1790 mL

0.8950 mL

1.7900 mL

10 mM

0.0895 mL

0.4475 mL

0.8950 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

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Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (2.24 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (2.24 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.24 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Working solution concentration: 0.22 mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact

MedChemExpress (MCE) .

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (298 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Kumar KG, et al. Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides. 2009 Oct;30(10):1892-900. [Content Brief]

[2]. Kievit P, et al. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes. 2013;62(2):490-497. [Content Brief]

[3]. Peng J, et al. Setmelanotide-mediated MC4R activation improves hypothalamic obesity via CaMKK2/AMPK pathways. Front Pharmacol. 2026;16:1730786. Published 2026 Jan 12. [Content Brief]

[4]. Sharma S, et al. Current Mechanistic and Pharmacodynamic Understanding of Melanocortin-4 Receptor Activation. Molecules. 2019;24(10):1892. Published 2019 May 16. [Content Brief]

[5]. Amorim MR, et al. Melanocortin receptor 4 agonist setmelanotide treats opioid-induced respiratory depression. bioRxiv [Preprint]. 2026 Mar 10:2026.03.08.708886. doi: 10.64898/2026.03.08.708886. PMID: 41959165; PMCID: PMC13061029. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
H₂O / DMSO	1 mM	0.8950 mL	4.4750 mL	8.9501 mL	22.3752 mL
	5 mM	0.1790 mL	0.8950 mL	1.7900 mL	4.4750 mL
	10 mM	0.0895 mL	0.4475 mL	0.8950 mL	2.2375 mL
	15 mM	0.0597 mL	0.2983 mL	0.5967 mL	1.4917 mL
	20 mM	0.0448 mL	0.2238 mL	0.4475 mL	1.1188 mL
	25 mM	0.0358 mL	0.1790 mL	0.3580 mL	0.8950 mL
	30 mM	0.0298 mL	0.1492 mL	0.2983 mL	0.7458 mL
	40 mM	0.0224 mL	0.1119 mL	0.2238 mL	0.5594 mL
	50 mM	0.0179 mL	0.0895 mL	0.1790 mL	0.4475 mL
DMSO	60 mM	0.0149 mL	0.0746 mL	0.1492 mL	0.3729 mL
DMSO	80 mM	0.0112 mL	0.0559 mL	0.1119 mL	0.2797 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Setmelanotide

8 Cited Publications

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Setmelanotide

α-MSH

Melanotan (MT)-II

SHU 9119

Melanotan I

Bremelanotide Acetate

THIQ

Bremelanotide

JNJ-10229570

Semaglutide

Azelaprag

Octreotide

Venetoclax

Publications Citing Use of MedChemExpress (MCE) Setmelanotide

All Melanocortin Receptor Isoforms

All Calmodulin Isoforms

All AMPK Isoforms

Biological Activity

Chemical Information

Publications (8)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Setmelanotide

α-MSH

Melanotan (MT)-II

SHU 9119

Melanotan I

Bremelanotide Acetate

THIQ

Bremelanotide

JNJ-10229570

Semaglutide

Azelaprag

Octreotide

Venetoclax

Publications Citing Use of MedChemExpress (MCE) Setmelanotide

All Melanocortin Receptor Isoforms

All Calmodulin Isoforms

All AMPK Isoforms

Biological Activity

Chemical Information

Publications (8)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Setmelanotide Related Classifications

HY-19870 Related Classifications