FDA Approved

Setmelanotide

Hormonal & Endocrine · RM-493, IRC-022493, Imcivree

A synthetic cyclic octapeptide melanocortin-4 receptor (MC4R) agonist studied in the leptin-melanocortin signaling pathway and in rare monogenic disorders of energy homeostasis.

🔬 Research use only — not for human or veterinary use. K4 Elite does not provide dosing instructions.

Molecular Formula

C49H68N18O9S2

Molecular Weight

1117.32 g/mol

PubChem

CID 11993702 ↗

Research Level

FDA Approved

Browse the store →

Setmelanotide is a synthetic cyclic octapeptide that acts as an agonist at the melanocortin-4 receptor (MC4R), a G-protein-coupled receptor central to the hypothalamic leptin-melanocortin pathway involved in energy balance signaling. It was granted U.S. FDA approval in 2020 under the trade name Imcivree for chronic weight management in specific rare monogenic conditions.

Research interest centers on individuals with genetic variants upstream of MC4R - including pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), and leptin receptor (LEPR) deficiencies - where melanocortin signaling is impaired. In these settings the peptide is studied as a pharmacologic agonist that engages MC4R downstream of the defective gene.

Setmelanotide binds and activates MC4R, a class A GPCR expressed in hypothalamic neurons. Receptor activation is coupled to Gas and adenylate cyclase, raising intracellular cAMP in studies of melanocortin signaling. Investigators describe this as re-engaging a signaling node that lies downstream of leptin, POMC processing, and PCSK1 cleavage.

Because the peptide acts at the receptor level, preclinical and clinical research has examined it in models where upstream components of the pathway are genetically disrupted.

Melanocortin pathway signaling - studied as an MC4R agonist within the leptin-melanocortin axis [1][2].
Monogenic energy-homeostasis disorders - investigated in POMC, PCSK1, and LEPR deficiency populations [2].
Syndromic obesity models - examined in Bardet-Biedl syndrome research cohorts [1].
Receptor pharmacology and safety signals - characterized for on-target effects such as skin pigmentation in study reports [3].

📋 How published studies were conducted — a research reference summarizing study designs from the literature. This is not usage, dosing, or administration guidance. K4 Elite does not provide dosing instructions; determining any research protocol is the sole responsibility of the qualified researcher.

In two single-arm, open-label, multicentre phase 3 trials, investigators administered setmelanotide to participants with severe obesity attributed to POMC or LEPR deficiency and measured the proportion achieving at least 10% weight reduction at approximately one year; the study reported roughly 80% of POMC and 45% of LEPR participants meeting that threshold [2].

In the VENTURE phase 3 trial, researchers studied children aged 2-5 years with MC4R-pathway-associated obesity over a 1-year open-label period and reported changes in body-mass-index metrics [1].

The NIH LiverTox monograph summarizes the reported adverse-event profile from the clinical program, including injection-site reactions and hyperpigmentation [3].

Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.

LeptinNeutral

Setmelanotide acts downstream of leptin at MC4R; studied specifically where leptin signaling is genetically impaired.

PT-141 (Bremelanotide)Neutral

Both are melanocortin-receptor agonists but studied for different receptor subtypes and research questions.

Melanotan IICaution

Both engage melanocortin receptors and can affect pigmentation pathways in study reports; not studied in combination.

What receptor does setmelanotide target?

Published research characterizes it as an agonist at the melanocortin-4 receptor (MC4R) within the leptin-melanocortin signaling pathway [1][2].

Why is it studied in genetic obesity?

It acts downstream of genes such as POMC, PCSK1, and LEPR, so researchers investigate it in models where those upstream components are disrupted [2].

Is this product intended for human use?

No. This entry is provided for research and informational purposes only. Nothing here is dosing guidance or a therapeutic recommendation.

Disclaimer: This profile summarizes published preclinical and laboratory research for reference only. It is not medical advice and makes no claim of safety or efficacy in humans. Determining any research protocol is the sole responsibility of the qualified researcher. Products are sold strictly for in-vitro research and have not been evaluated by the FDA.