Cat. No.: HY-19870A

Copy Link Print Information

Setmelanotide TFA

Name: Setmelanotide TFA
Brand: MedChemExpress
SKU: HY-19870A
Availability: PreOrder

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

8 Cited Publications

Customer Review

Based on 8 publication(s) in Google Scholar

Setmelanotide TFA (RM-493 TFA) is a blood-brain barrier-permeable, selective MC4R agonist with a K_i value of 2.1 nM for hMC4R. Setmelanotide TFA activates the CaMKK2/AMPK signaling pathway. Setmelanotide TFA 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 TFA is applicable to research related to obesity, hyperinsulinemia, fatty liver and respiratory depression.

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

Formula: C₅₁H₆₉F₃N₁₈O₁₁S₂
Molecular Weight:1231.33

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Setmelanotide TFA Chemical Structure

Size

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

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
Chemical Information
Publications (8)
Purity & Documentation
References
Calculators
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 TFA (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 TFA (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].
TFA of Setmelanotide (6.4 μmol; intraperitoneal injection; single dose) acutely improves glucose clearance in leptin-deficient obese and glucose-intolerant C57BL/6J mice^[1].
TFA 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].
TFA 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].
TFA 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 TFA (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].
TFA 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].
TFA of Setmelanotide (100-500 nmol/kg; subcutaneous injection; single administration) suppresses food intake in fasted male Sprague-Dawley rats^[4].
TFA 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].
TFA 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.

Chemical Information

Molecular Weight 1231.33
Formula C₅₁H₆₉F₃N₁₈O₁₁S₂
Synonyms

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

Please store the product under the recommended conditions in the Certificate of Analysis.

Publications (8)

All In Vivo Efficacy StudyBio/Physico-chemical Assay

Sort by:

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 TFA 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 TFA 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 TFA 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 TFA 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 TFA 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.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (276 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]

Calculators

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)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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.

Bioz

Setmelanotide TFA

8 Cited Publications

100 mg Get Quote

Subscribe to the

MedChemExpress

Newsletter

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

Setmelanotide TFA

Publications Citing Use of MedChemExpress (MCE) Setmelanotide TFA

All Melanocortin Receptor Isoforms

All Calmodulin Isoforms

All AMPK Isoforms

Biological Activity

Chemical Information

Publications (8)

Purity & Documentation

References

Calculators

Help & FAQs

Setmelanotide TFA Related Classifications

HY-19870A Related Classifications

Bioz