Setmelanotideindication Setmelanotide is a targeted peptide therapy that represents a significant advancement in treating specific genetic forms of obesitySetmelanotide is a small-peptide, melanocortin-4 receptor (MC4R) agonist, developed by Rhythm for the treatment of obesity due to proopiomelanocortin (POMC) .... As a selective melanocortin-4 receptor (MC4R) agonist, Setmelanotide works by activating a crucial pathway in the body that regulates appetite and energy balance. This mechanism offers a novel approach to chronic weight management, particularly for individuals whose obesity stems from rare genetic deficiencies affecting the MC4R pathwaySetmelanotideis an agonist of melanocortin receptors, with approximately 20-fold selectivity for the melanocortin 4 receptor subtype..
Setmelanotide, marketed under the brand name Imcivree, is a pharmaceutical compound that acts as a peptide-based agonist.Setmelanotide (trifluoroacetate salt) Its primary indication is for chronic weight management in patients two years of age and older who have obesity due to specific genetic disorders. These include deficiencies in pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or Bardet-Biedl syndrome, all of which disrupt the MC4R signaling pathway. By targeting the root cause of these rare genetic forms of obesity, Setmelanotide aims to restore normal signaling, leading to improved satiety and weight-related outcomes.Setmelanotide | C49H68N18O9S2 | CID 11993702 - PubChem
The melanocortin-4 receptor (MC4R) plays a pivotal role in the central regulation of energy homeostasis.CAS 920014-72-8 (Setmelanotide) When activated by endogenous melanocortin peptides like alpha-melanocyte-stimulating hormone ($\alpha$-MSH), MC4R signals satiety and promotes energy expenditure. In individuals with genetic defects in POMC or PCSK1, or mutations affecting the MC4R receptor itself, this signaling pathway is impaired, leading to increased hunger and reduced feelings of fullness.Indicated for long-term weight management in patients with obesityowing to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), ... Setmelanotide is designed as a cyclic peptide analogue of $\alpha$-MSH, specifically engineered to act as a potent and selective agonist for the MC4R. This targeted action helps to bypass the genetic blockages, thereby reactivating the MC4R pathway. Studies have shown Setmelanotide to have high binding affinity and efficacy at the MC4R, demonstrating its ability to increase cAMP production in cells expressing the receptor. This activation helps to restore the body's natural ability to regulate appetite and promote weight loss.2023年7月9日—Setmelanotide (Imcivree ®) is one of the costliest medications to treat obesity. This is a melanocortin 4 receptor (MC4R) agonist indicated ...
Setmelanotide is FDA-approved for long-term weight management in patients with obesity stemming from specific genetic conditionsSetmelanotide is an 8 amino acid cyclic peptide analogof endogenous melanocortin peptide α-MSH (alpha-melanocyte stimulating hormone). The chemical name .... These include:
* POMC Deficiency: Caused by mutations in the POMC gene, leading to a lack of functional POMC protein, which is a precursor to appetite-regulating hormones.
* PCSK1 Deficiency: Resulting from mutations in the PCSK1 gene, which impairs the processing of POMC and other prohormones.
* Bardet-Biedl Syndrome (BBS): A rare genetic disorder that affects multiple body systems and is often associated with severe obesity due to MC4R pathway dysfunction.
* LEPR Deficiency: While less commonly cited in initial approvals, research has also explored Setmelanotide's efficacy in patients with leptin receptor (LEPR) deficiency obesity, another condition impacting appetite regulation.
The drug is indicated for both adults and children aged 12 years and older.Imcivree vs. Wegovy for Weight loss - GoodRx For younger children (two years and older) with POMC or PCSK1 deficiency, it is also approved.Setmelanotide is an 8 amino acid cyclic peptide analogof endogenous melanocortin peptide α-MSH (alpha-melanocyte stimulating hormone). The chemical name ... Dosing regimens are tailored based on age and the specific genetic indication. For instance, adults and adolescents (12-17 years) may start with a 1 mg subcutaneous injection daily for two weeks, with potential dose adjustments thereafter.
Clinical trials have demonstrated the efficacy of Setmelanotide in inducing significant weight loss and improving metabolic parameters in patients with these rare genetic obesity conditionsSetmelanotide (RM-493, BIM-22493, CAM 4072)is a cyclic peptide full agonist of melanocortin-4 receptor (MC4R) with an EC50 of 0.27 nM and a Ki of 2.1 nM.. Studies have shown that Setmelanotide can lead to substantial reductions in body weight, improved body mass index (BMI), and enhanced satiety scores. For example, a Phase 2 trial indicated that Setmelanotide, as an MC4R peptide agonist, reduced weight in patients with LEPR deficiency obesity. Furthermore, meta-analyses evaluating the efficacy and safety of Setmelanotide for weight loss in severe obesity linked to MC4R deficiency have highlighted its promising benefits in improving satiety and weight-related outcomesSetmelanotide. The drug's ability to target the underlying genetic cause offers a more effective and sustained approach compared to treatments that do not address the root molecular defect.Setmelanotide - LiverTox - NCBI Bookshelf - NIH
As with any medication, Setmelanotide has potential side effectsSetmelanotide (trifluoroacetate salt). Common adverse reactions reported include injection site reactions, headache, and nausea. More serious potential side effects can include darkening of the skin and gums (hyperpigmentation), spontaneous erections (priapism) in males, and mood changes, including depression and suicidal ideation. Due to these risks, patients are closely monitored by healthcare professionals. The drug's safety profile is evaluated regularly, and prescribers are advised to counsel patients on potential risks and benefits. Liver toxicity has also been a focus of investigation; however, current information from resources like the NIH's LiverTox indicates ongoing monitoring.Indicated for long-term weight management in patients with obesityowing to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), ...
Setmelanotide occupies a unique niche in the landscape of weight-loss treatments. Unlike broader-acting weight-loss medications such as semaglutide (e.g., Wegovy) or tirzepatide, which are designed for general obesity or overweight individuals, Setmelanotide is specifically indicated for rare genetic disorders. While semaglutide and similar drugs act on GLP-1 receptors, Setmelanotide's mechanism targets the MC4R pathway, addressing a distinct biological cause of obesity. This specificity makes Setmelanotide a critical therapeutic option for a population that has historically had limited or no effective treatment options for their specific genetic conditions. The cost of Setmelanotide is notably high, reflecting its specialized nature, R&D investment, and the limited patient population it serves. This high cost is a significant consideration for access and affordability.
Research continues to explore the full potential of Setmelanotide and other MC4R agonists. This includes investigating its efficacy in a wider range of genetic obesity subtypes, optimizing dosing and delivery methods (such as sustained-release formulations), and further understanding its long-term safety profile. The development of peptide-based therapies like Setmelanotide also opens doors for the creation of novel drug candidates that can cross the blood-brain barrier more effectively or offer improved pharmacokinetic propertiesSetmelanotide, 920014-72-8. As our understanding of the genetic underpinnings of obesity deepens, targeted therapies like Setmelanotide are poised to play an increasingly vital role in personalized medicine for weight management.Carbocyclic setmelanotide analogs maintain biochemical ...
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