Retatrutide (60mg – 1200mg)

Retatrutide

Cost per milligram	$2.53 – $5.70
Purity	99.72%
Certified Endotoxin-safe	Yes
Independently Tested	Yes

• 30mg Vials
  • Peptide Partners Manufacturer ID: VI32
  • Batch ID: RP260130

Research Studies

(for educational purposes only)

Study 1: Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide

Authors: Wenzhuo Li, Qingtong Zhou, Zhaotong Cong, Qingning Yuan, Wenxin Li, Fenghui Zhao, H. Eric Xu, Li-Hua Zhao, Dehua Yang & Ming-Wei Wang

Source: https://www.nature.com/articles/s41421-024-00700-0

Scientific Findings

This study utilized cryo-electron microscopy to elucidate the structural basis of Retatrutide’s triple agonism at the GLP-1, GIP, and GCG receptors. The researchers determined the structures of Retatrutide in complex with each of the three receptors, revealing that the peptide adopts a single continuous helix. The triple agonism is achieved through a combination of conserved interactions and receptor-specific contacts within the transmembrane domain. The study identified key residues and structural features, such as the conformation of extracellular loop 1 (ECL1) in GIPR, that contribute to the differential binding and activation of the receptors. Mutagenesis and cAMP signaling assays confirmed the functional importance of these interactions, providing a molecular blueprint for Retatrutide’s potent and balanced activity.

Plain English Interpretation

Scientists have figured out how the new weight-loss drug, Retatrutide, works at a molecular level. This drug is unique because it can activate three different hormone receptors in the body that control appetite and metabolism. Using powerful microscopes, the researchers took detailed 3D pictures of Retatrutide as it was bound to each of these three receptors. They discovered that the drug uses a clever strategy of both sticking to parts that all three receptors have in common and also making specific connections with unique parts of each receptor. This allows it to effectively ‘talk’ to all three at once, leading to its powerful effects on weight loss and blood sugar control. Understanding this mechanism helps to explain why Retatrutide is so effective and can guide the development of even better medicines in the future.

Study 2: Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids

Authors: Yi Wen, Deven Lemen, Yanzhu Lin, Yan Q Chen, Ajit Regmi, William C Roell, Melissa K Thomas, Mark L Hartman, Tamer Coskun, Zvonko Milicevic, Axel Haupt, Giacomo Ruotolo, Robert J Konrad

Source: https://pubmed.ncbi.nlm.nih.gov/40726454/

Scientific Findings

This study investigated the effect of Retatrutide on circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and its relationship with serum lipid levels. The study included both in vivo analysis from two phase 2 clinical trials and in vitro experiments using primary human hepatocytes. The in vitro component demonstrated that both glucagon and Retatrutide directly decreased ANGPTL3/8 secretion from hepatocytes, and this effect was blocked by a glucagon receptor (GCGR) antagonist. These findings suggest that the GCGR agonism of Retatrutide contributes to the reduction in circulating ANGPTL3/8, which in turn may lead to lower triglyceride and LDL-cholesterol levels.

Plain English Interpretation

Researchers explored how Retatrutide, a new drug for diabetes and obesity, helps lower bad fats in the blood. They found that Retatrutide reduces the levels of a protein complex called ANGPTL3/8, which is known to increase fats like triglycerides and LDL cholesterol. To understand how this happens, they conducted experiments on human liver cells in a lab dish. They discovered that Retatrutide directly acts on these cells to decrease the secretion of ANGPTL3/8. This suggests that part of Retatrutide’s effectiveness in improving cholesterol levels comes from its direct action on the liver, providing a clearer picture of how this promising new drug works.

Study 3: Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP

Authors: Xin Cui, Yueming Zhu, Lidan Zeng, Mengyuan Zhang, Amad Uddin, Theresa W Gillespie, Lauren E McCullough, Shaying Zhao, Mylin A Torres, Yong Wan

Source: https://pubmed.ncbi.nlm.nih.gov/39868848/

Scientific Findings

This study elucidates a molecular mechanism by which Retatrutide overcomes therapeutic resistance in obese triple-negative breast cancer (TNBC). The research identifies a dysfunctional EIF3H/YAP proteolytic axis as a key mediator between cancer-associated adipocytes and drug response. In vitro experiments demonstrated that cancer-associated adipocytes upregulate the hexosamine biosynthetic pathway (HBP), leading to O-GlcNAcylation and stabilization of the YAP protein. Retatrutide was found to inhibit the HBP, thereby preventing YAP O-GlcNAcylation and promoting its degradation. This, in turn, suppresses tumor growth and enhances chemotherapy efficacy. The study provides a detailed mechanistic insight into the interplay between metabolic reprogramming, protein stability, and drug response in the context of obesity and cancer.

Plain English Interpretation

Scientists have discovered how the weight-loss drug Retatrutide can also help treat a type of breast cancer that is more common in obese patients. They found that fat cells near the tumor can make the cancer cells resistant to treatment. These fat cells cause a change in the cancer cells’ metabolism, which leads to the buildup of a protein called YAP that helps the cancer grow. The researchers showed that Retatrutide can reverse this process. In lab experiments, Retatrutide blocked the metabolic changes caused by the fat cells and caused the YAP protein to be destroyed. This made the cancer cells more sensitive to chemotherapy. This research uncovers a new way that obesity affects cancer and suggests that drugs like Retatrutide could be used to improve cancer treatment in obese patients.