Retatrutide, CAS number 2381089-83-2

Retatrutide is a groundbreaking triple agonist targeting the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. This novel compound, unveiled by Eli Lilly in June 2023, is engineered to address obesity and type 2 diabetes through a multifaceted approach that enhances receptor activation for superior blood sugar regulation and weight management. Clinical studies have shown promising results, with a 48-week phase 2 obesity trial revealing significant weight reductions of 22.8% and 24.2% at 8 and 12 mg doses, respectively.

Retatrutide represents a new frontier in peptide therapy, designed as a fusion peptide acting on multiple receptors. This innovative approach allows for broad therapeutic applications and potential label extensions post-approval. The compound's development builds on the success of dual agonists like Tirzepatide (Mounjaro), with Retatrutide offering enhanced efficacy through its triple receptor activity.

Basic Information

• Chemical name: Retatrutide
• CAS Registration Number: 2381089-83-2
• Molecular formula: C187H281N43O60
• Molecular Weight: 4,731.33 g/mol

Clinical trials have demonstrated Retatrutide's significant impact on glucose and weight management. A phase 2 trial published in June 2023 in The New England Journal of Medicine reported weight loss of 17.5% at week 24 and 24.2% at week 48 for the 12 mg dose group. A phase 2 trial published in August 2023 in The Lancet highlighted superior efficacy in reducing HbA1c and body weight compared to Dulaglutide. Retatrutide is also under investigation for various other indications, including metabolic-associated fatty liver disease (MASLD), obstructive sleep apnea, and knee osteoarthritis, with ongoing phase 3 trials.

PS Chemical Consortium employs state-of-the-art synthetic techniques to produce Retatrutide, ensuring the highest quality and efficacy. Our production process includes:

Peptide Synthesis

• Raw Material Preparation: High-purity amino acid monomers and linkers (e.g., H-AEEA) are prepared to ensure the final product's quality.
• Solid Phase Peptide Synthesis (SPPS): This method involves sequentially adding amino acid monomers to a solid support, forming peptide bonds. Each step includes washing, deprotection, and coupling to ensure precision and efficiency.
• Side Chain Modification: Fatty acid chains and other side groups are introduced via chemical modification, enhancing the peptide's stability and activity.

Purification and Characterization

• Purification: Techniques such as gel filtration, ion exchange chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC) are used to achieve high purity.
• Characterization: Comprehensive analysis, including mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD) spectroscopy, and bioactivity assays, confirms the peptide's structure and function.

Retatrutide's peptide sequence is meticulously crafted to optimize its therapeutic effects. Key structural features include:

• A Glycine (G) residue at position 3, and a non-natural amino acid, aMeL (α-methyl-L-leucine), at position 13 to enhance receptor activity.
• A Lysine (K) residue at position 17, modified with AEEA and γ-Glutamic acid (γGlu) linkers to introduce a bivalent fatty acid side chain, extending its activity in the body.
• Aib (α-aminoisobutyric acid) at position 20 to prevent degradation by dipeptidyl peptidase-4 (DPP4).
• Glutamic acid (E) at positions 24 and 28, and Tyrosine (Y) at position 25 for optimized receptor interaction.