2. GPCR/G Protein Neuronal Signaling Membrane Transporter/Ion Channel Epigenetics PI3K/Akt/mTOR
  3. Melanocortin Receptor Calmodulin AMPK
  4. Setmelanotide monoacetate

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

Cat. No.: HY-19870C Purity: 99.88%
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Setmelanotide monoacetate (RM-493 monoacetate) is a blood-brain barrier-permeable, selective MC4R agonist with a Ki value of 2.1 nM for hMC4R. Setmelanotide monoacetate activates the CaMKK2/AMPK signaling pathway. Setmelanotide monoacetate 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 monoacetate is applicable to research related to obesity, hyperinsulinemia, fatty liver and respiratory depression.

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

Custom Peptide Synthesis

CAS No. : 2759937-80-7

Size Price Stock Quantity
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10 mM * 1 mL in DMSO
ready for reconstitution
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Based on 8 publication(s) in Google Scholar

Other Forms of Setmelanotide monoacetate:

Setmelanotide monoacetate Related Antibodies

Top Publications Citing Use of Products

    Setmelanotide monoacetate 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.

    Setmelanotide monoacetate 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 MC4RPVH neurons.

    Setmelanotide monoacetate 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 Mc4rfl/fl mice.

    Setmelanotide monoacetate 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 monoacetate 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.

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    Description

    Setmelanotide monoacetate (RM-493 monoacetate) is a blood-brain barrier-permeable, selective MC4R agonist with a Ki value of 2.1 nM for hMC4R. Setmelanotide monoacetate activates the CaMKK2/AMPK signaling pathway. Setmelanotide monoacetate 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 monoacetate is applicable to research related to obesity, hyperinsulinemia, fatty liver and respiratory depression[1][2][3][4][5].

    IC50 & Target[4]

    MC4R

    2.1 nM (Ki)

    MC1R

    3.9 nM (Ki)

    MC3R

    10 nM (Ki)

    MC5R

    430 nM (Ki)

    In Vitro

    Setmelanotide binds to hMC1R, MC3R, MC4R and rat MC4R with high affinity, while it shows weak binding affinity to hMC5R[1].
    Setmelanotide monoacetate (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 Ki 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.

    Setmelanotide monoacetate Related Antibodies
    In Vivo

    Setmelanotide monoacetate (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 monoacetate (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.
    Molecular Weight

    1177.36

    Formula

    C51H72N18O11S2
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    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)

    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (84.94 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 0.8494 mL 4.2468 mL 8.4936 mL
    5 mM 0.1699 mL 0.8494 mL 1.6987 mL
    View the Complete Stock Solution Preparation Table

    * 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.

    • Molarity Calculator

    • Dilution Calculator

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

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    Volume (start)

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    In Vivo:

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

    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 (2.12 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.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

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

      Solubility: ≥ 2.5 mg/mL (2.12 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.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

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

    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).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.88%

    SDS (252 KB)

    COA (258 KB) RP-HPLC (109 KB) MS (219 KB)

    Handling Instructions (2659 KB)
    References

    Complete Stock Solution Preparation Table

    * 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.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 0.8494 mL 4.2468 mL 8.4936 mL 21.2339 mL
    5 mM 0.1699 mL 0.8494 mL 1.6987 mL 4.2468 mL
    10 mM 0.0849 mL 0.4247 mL 0.8494 mL 2.1234 mL
    15 mM 0.0566 mL 0.2831 mL 0.5662 mL 1.4156 mL
    20 mM 0.0425 mL 0.2123 mL 0.4247 mL 1.0617 mL
    25 mM 0.0340 mL 0.1699 mL 0.3397 mL 0.8494 mL
    30 mM 0.0283 mL 0.1416 mL 0.2831 mL 0.7078 mL
    40 mM 0.0212 mL 0.1062 mL 0.2123 mL 0.5308 mL
    50 mM 0.0170 mL 0.0849 mL 0.1699 mL 0.4247 mL
    60 mM 0.0142 mL 0.0708 mL 0.1416 mL 0.3539 mL
    80 mM 0.0106 mL 0.0531 mL 0.1062 mL 0.2654 mL
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    Setmelanotide monoacetate Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Setmelanotide monoacetate2759937-80-7RM-493 monoacetate BIM-22493 monoacetate IRC-022493 monoacetateMelanocortin ReceptorCalmodulinAMPKMC ReceptorCaMCalcium-Modulated ProteinAMP-activated protein kinasePVN MC4R neuronsSprague-Dawley ratsMC4RC57BL/6J micerhesus macaquesmelanocortin-4 receptorcynomolgus monkeysHEK293 cellsCHO-K1 cellsCaMKK2/AMPK signaling pathwayInhibitorinhibitorinhibit

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