Shaanxi BLOOM Tech Co., Ltd. is one of the most experienced manufacturers and suppliers of liraglutide powder cas 204656-20-2 in China. Welcome to wholesale bulk high quality liraglutide powder cas 204656-20-2 for sale here from our factory. Good service and reasonable price are available.
Liraglutide powder , molecular formula C172H265N43O51, CAS 204656-20-2, molecular weight 1209.40. It is an artificially synthesized acylated human glucagon like peptide-1 (GLP-1) analogue with over 97% sequence similarity compared to natural GLP-1. Can be dissolved in water, ethanol, and propylene glycol. The 34th lysine position of the natural GLP-1 molecule is replaced by arginine, which not only preserves and prolongs the binding time between acylation products and proteins, but also significantly overcomes the disadvantage of easy degradation of GLP. Under normal storage conditions, it exhibits good stability, and its aqueous solution can maintain physical and chemical stability for at least 2 years.
Our product
Liraglutide COA
Glucagon-like peptide-1 is a core endogenous active polypeptide that regulates blood glucose and appetite in humans. However, the native molecule is rapidly degraded by dipeptidyl peptidase 4 (DPP-4), with an extremely short half-life of only 2 minutes, making it unsuitable for direct clinical administration. As the first-generation long-acting glucagon-like peptide-1 receptor agonist, liraglutide undergoes molecular modification via covalent conjugation with a 16-carbon palmitoyl fatty acid side chain, completely resolving the short-acting limitation of native GLP-1. Commercially available liraglutide powder serves as the key active pharmaceutical ingredient (API) for preparing clinical injectable formulations; its lyophilized powder form and intact molecular modification directly determine the long-acting performance of the drug.
Critical Drawbacks of Native GLP-1 and the Necessity of Molecular Modification
Endogenous glucagon-like peptide-1 is secreted by the intestinal tract after meals. It stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon release, delays gastric emptying and curbs appetite, exerting multiple pharmacological activities including hypoglycemic, weight-lowering and cardiovascular protective effects. It represents an ideal therapeutic target for metabolic diseases. Nevertheless, native GLP-1 has unavoidable clinical flaws: the alanine residue at the molecular terminus is specifically cleaved by endogenous DPP-4. Once entering the bloodstream, it becomes fully inactivated within mere minutes.
Direct administration requires continuous intravenous infusion, leading to extremely poor patient compliance and failing to meet long-term treatment demands for chronic diseases.
Three mainstream modification strategies are adopted in the industry to prolong the in vivo duration of polypeptide drugs: amino acid site mutation, polypeptide chain extension and fatty acid side chain modification. Among them, covalent fatty acid modification stands out as the optimal solution for long-acting polypeptide preparation, as it preserves core pharmacological activity, features stable modification processes and delivers remarkable long-acting efficacy gains.
As an industrially mass-produced lyophilized polypeptide API, it is accurately conjugated with a palmitic acid fatty acid chain at the terminal of solid-phase synthesis without altering the original core amino acid sequence of glucagon-like peptide-1. It retains 100% of the original pharmacological activity while achieving a leapfrog extension of half-life from 2 minutes to 13 hours, enabling once-daily subcutaneous injection to cover full-day therapeutic needs.
Principles of Molecular Structural Design
Precise Modification Site: Balancing Activity Retention and Long-Acting Optimization
Liraglutide retains 97% of the amino acid sequence of native glucagon-like peptide-1, with site-specific modification only at the 34th lysine residue. A 16-carbon saturated palmitoyl fatty acid chain is covalently attached to the polypeptide surface via a glutamate linker. This modification site has been validated by extensive pharmacological studies: it is distant from the core glucagon-like peptide-1 receptor-binding domain, so it does not hinder drug-receptor binding and fully preserves core pharmacological effects such as insulin secretion stimulation and appetite suppression.
Meanwhile, the modification site is exposed on the outer surface of the polypeptide, allowing the fatty acid chain to freely bind to human serum albumin and maximize sustained-release efficacy.
Rationale for Selecting the 16-Carbon Fatty Acid Chain
After comparing the modification effects of fatty acids with carbon chain lengths of 12, 14, 16 and 18 carbons, researchers confirmed that 16-carbon palmitic acid is the optimal chain length for liraglutide. Chains that are too short exhibit insufficient albumin binding affinity, resulting in rapid drug clearance.
Excessively long carbon chains drastically elevate polypeptide hydrophobicity and drastically reduce liraglutide water solubility, which not only impairs reconstitution of the API powder but also increases the risk of adverse reactions at injection sites. The 16-carbon fatty acid achieves a perfect balance between water solubility and protein binding rate, compatible with lyophilized powder formulation processes and human administration requirements.
Three Core Long-Acting Mechanisms of Fatty Acid Modification
1. Blockage of Enzymatic Cleavage Sites to Resist DPP-4 Degradation
This is the fundamental long-acting mechanism of fatty acid modification.
The N-terminus of native glucagon-like peptide-1 acts as a specific recognition site for DPP-4. After liraglutide is conjugated with a fatty acid chain, the large lipid side chain creates steric hindrance that wraps the enzyme-sensitive region of the polypeptide, preventing DPP-4 from approaching and cleaving the peptide chain. From the moment liraglutide powder is reconstituted into injection solution and enters human blood circulation, the drug molecule avoids rapid degradation at the source, greatly increasing the proportion of intact parent drug retained in blood.
2. Reversible Albumin Binding for Slow In Vivo Sustained Release
Human plasma contains abundant endogenous albumin capable of binding free lipid molecules. The palmitoyl fatty acid chain on the liraglutide molecule has a hydrophobic structure and undergoes reversible non-covalent binding with hydrophilic albumin upon entering the bloodstream. Bound liraglutide molecules gain substantially increased molecular volume, preventing rapid glomerular filtration and excretion by the kidneys and drastically slowing drug clearance. This binding is a dynamic reversible process: when free drug concentration in blood declines, bound drug slowly dissociates to release active monomers that continuously activate glucagon-like peptide-1 receptors, generating sustained long-acting effects.
3. Subcutaneous Depot Effect to Extend Absorption Period
When an injection prepared from reconstituted liraglutide API powder is administered subcutaneously, the hydrophobic fatty acid chain forms a micro drug depot at the injection site. Instead of instant full entry into the bloodstream, the drug slowly permeates into circulation through interactions between the lipid chain and interstitial fluid. The superposition of three effects-albumin-mediated sustained release, anti-enzymatic degradation and subcutaneous depot formation-stabilizes liraglutide's in vivo half-life at 13 hours, with once-daily administration delivering steady 24-hour blood glucose control and weight loss outcomes.
The Key to Intact Fatty Acid-Modified Structure
Many users overlook the impact of API form on long-acting efficacy. Liquid liraglutide formulations are prone to hydrolysis and shedding of fatty acid side chains as well as peptide bond cleavage during long-term storage, directly abolishing long-acting properties. Commercially available liraglutide uniformly adopts sterile lyophilized powder as the API, whose core purpose is to protect the structural integrity of fatty acid modifications.
The lyophilization process removes water from raw materials under low-temperature vacuum conditions, avoiding side chain hydrolysis triggered by pH shifts and temperature fluctuations in liquid environments.
When stored hermetically under low temperatures, it maintains stable molecular structure over long-term storage, with no fatty acid side chain shedding or polypeptide sequence degradation. Signs of powder moisture absorption, yellowing or purity decline indicate damaged fatty acid-modified structures, accompanied by markedly shortened drug half-life and severely diminished clinical efficacy. Accordingly, the production process and storage conditions of the powder API serve as prerequisites for realizing the long-acting benefits of fatty acid modification.
Comparison of Modification Strategies with Other GLP-1 Polypeptide Drugs
As another long-acting GLP-1 agonist, semaglutide adopts dual-site modification with an 18-carbon fatty acid chain, delivering a longer half-life of up to 7 days suitable for once-weekly dosing. Liraglutide features single-site modification with a 16-carbon fatty acid chain; while its long-acting potency is weaker, it possesses a simpler molecular structure, lower synthesis difficulty for the API powder, fewer by-products and a lower incidence of gastrointestinal adverse reactions.
Both drugs rely on fatty acid modification to achieve long-acting effects, differing only in fatty acid carbon chain length and modification sites. Compared with long-acting polypeptides modified via amino acid mutation, fatty acid-modified liraglutide bears a molecular structure more similar to endogenous human GLP-1, carrying a lower risk of hypoglycemia and prominent safety advantages.
Core Mechanisms of Action
Glucose-Dependent Hypoglycemic Pathway
The drug specifically activates GLP-1 receptors on pancreatic β-cells, stimulating insulin secretion only when blood glucose is elevated. Simultaneously, it inhibits glucagon release from pancreatic α-cells and reduces hepatic gluconeogenesis to steadily control fasting and postprandial blood glucose with minimal hypoglycemia risk.
Metabolic Mechanism for Weight Regulation
It targets the hypothalamic feeding center to enhance satiety and reduce food cravings, while delaying gastric emptying to cut calorie intake.Long-term administration reduces visceral fat accumulation and regulates blood lipid levels for sustained weight loss.
Lipid chain-mediated sustained release maintains stable all-day blood drug concentrations to sustain long-term metabolic regulation.
Multi-Organ Protective Pharmacological Effects
Persistent activation of the GLP-1 pathway suppresses vascular inflammation and oxidative stress, protects vascular endothelium and lowers risks of cardiovascular complications; it also reduces hepatic lipid accumulation and ameliorates non-alcoholic fatty liver disease. Degraded impurities generated in API powder damage lipid-modified structures, directly impairing all pharmacological activities including hypoglycemia, weight loss and organ protection.
Liraglutide powder is an artificially synthesized acylated human glucagon like peptide-1 (GLP-1) analogue with over 97% sequence similarity compared to natural GLP-1.
The molecular structure of liraglutide includes the following main characteristics: the 34th lysine position of the natural GLP-1 molecule is replaced by arginine, which not only preserves and prolongs the binding time between acylation products and proteins, but also significantly overcomes the disadvantage of GLP's easy degradation.
An additional fatty acid side chain was added to the 26th lysine, which helps to prolong the half-life of acylation products in vivo. These unique molecular changes have made delilaglutide show outstanding effects in clinical treatment, especially in diabetes and weight loss.
The chemical methods for synthesizing liraglutide mainly include the following steps:
1. Fragment synthesis
Firstly, divide the entire liraglutide into several segments, which can generally be divided into five segments: 1st to 4th amino acids, 5th to 10th amino acids, 11th to 16th amino acids, 17th to 24th amino acids, and 25th to 31st amino acids. Each fragment is synthesized separately, which can reduce the difficulty and cost of peptide synthesis and improve synthesis efficiency.
For the synthesis of each fragment, solid-phase synthesis or liquid-phase synthesis methods are generally used. The solid-phase synthesis method involves connecting the carboxyl groups of amino acids to the resin, then sequentially adding the amino acids to the resin in sequence, and finally cutting off the peptides from the resin. The liquid-phase synthesis method involves dissolving all amino acids in an organic solvent and then condensing them in sequence to form peptide fragments.
2. Coupling reaction
Perform coupling reaction on the 5 peptide fragments synthesized in step 1 to form a complete Liraglutide. The coupling reaction can be carried out using chemical or biological coupling agents, and the specific method can be selected according to actual needs.
In the coupling reaction, it is necessary to connect the amino group of each fragment with the carboxyl group of the next fragment. To achieve this, it is usually necessary to use condensation agents such as DIC or BOP.
These condensation agents can promote the reaction between amino and carboxyl groups, forming peptide bonds. In the coupling reaction, attention should also be paid to controlling the reaction conditions, such as temperature, pH value, and reaction time, to ensure the smooth progress of the reaction.
3. Purification and identification
The synthesized liraglutide needs to be purified and identified to ensure the purity and quality of the product. Purification is usually carried out using methods such as high-performance liquid chromatography (HPLC) or electrophoresis, followed by identification using mass spectrometry, nuclear magnetic resonance, and other methods.
Through these means, it can be ensured that the molecular weight and sequence of the synthesized product are consistent with expectations, and there are no impurities or by-product residues.
4. Other modifications
In addition to the above steps, sometimes other modifications are required, such as adding or removing protective groups. These steps are also essential as they can protect the active groups in peptides from being destroyed or side reactions occur, improving the quality and yield of synthesized Liraglutide powder.
The above are the main chemical methods for synthesizing liraglutide, but of course, some details and techniques need to be noted in practical operation. For example, selecting the appropriate solvent system, controlling temperature and pH, and using appropriate catalysts can all affect synthesis efficiency and product quality. Therefore, in practical operation, adjustments and optimizations need to be made according to specific circumstances.
1. RP-HPLC for Purity and Related Substances Testing
Reversed-phase high-performance liquid chromatography serves as the core quality control method. A polypeptide-specific C18 chromatographic column is used with gradient elution of buffer salt and acetonitrile, and UV detection at 210 nm. The main peak purity is quantified, while deamidated peptides, truncated peptides and impurities with shed fatty acid side chains are accurately detected, complying with impurity limit specifications set by pharmacopoeias worldwide. This is a core release test item for APIs.
2. LC-MS for Structural Identification and Impurity Tracing
Liquid chromatography-mass spectrometry (LC-MS) performs qualitative confirmation. Primary mass spectrometry verifies the exact molecular weight, and secondary fragment mass spectrometry validates the complete amino acid sequence and palmitoyl modification sites. It rapidly distinguishes unmodified polypeptide impurities, judges whether the molecular structure of lyophilized powder remains intact, and supports raw material authenticity identification and tracing of process-related impurities.
3. Physicochemical and Safety Index Testing
Karl Fischer titration for water content to control powder degradation caused by moisture absorption
ICP-MS for heavy metal detection (lead, arsenic, mercury, etc.)
Headspace gas chromatography for residual organic solvents from synthesis
Membrane filtration method for microbial limit testing
Limulus amebocyte lysate (LAL) assay for bacterial endotoxin detection All tests meet safety standards for injectable-grade APIs.
4. In Vitro Biological Activity Assay
A cell model overexpressing GLP-1 receptors is adopted to detect receptor activation via fluorescence signals. Biological potency is calculated by comparison with reference standards to directly verify the integrity of fatty acid modification and drug efficacy. Combined with accelerated stability testing, this method evaluates long-term impacts of temperature, humidity and light on powder purity and biological activity.
FAQ
Is liraglutide the same as Ozempic?
+
-
Liraglutide and Ozempic are not the same medication. While both belong to the same drug class (GLP-1 receptor agonists) and work similarly by suppressing appetite and regulating blood sugar, they feature different active ingredients and dosing schedules.
Why is liraglutide not as popular?
+
-
The higher rates of discontinuation for liraglutide compared with some other obesity medications due to adverse effects may limit its use in some patient populations. Also, liraglutide is an injectable medication with a high monthly cost.
Hot Tags: liraglutide powder cas 204656-20-2, suppliers, manufacturers, factory, wholesale, buy, price, bulk, for sale, Epitalon Powder CAS 307297 39 8, Selank Peptide CAS 129954 34 3, Bremelanotide Powder CAS 189691 06 3, GLP 1 Peptide CAS 87805 34 3, Best Growth Hormone Releasing Peptide CAS 87616 84 0, Lpamorelin Powder CAS 170851 70 4