Description

Product Description

Pemvidutide TFA (ALT-801, trifluoroacetate salt) represents one of the most advanced dual-incretin peptides currently under investigation. It is designed to activate both glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), providing a unique pharmacological balance between glucose regulation, appetite suppression, and lipid metabolism.

Background and Rationale

The global epidemic of obesity and non-alcoholic steatohepatitis (NASH) has become a critical public health challenge. According to recent estimates, more than 650 million adults worldwide suffer from obesity, and up to 25% of the adult population may have non-alcoholic fatty liver disease (NAFLD), with NASH being the progressive and more harmful form. Traditional therapies, such as lifestyle modification, GLP-1 analogues, and bariatric surgery, have shown benefits but remain insufficient to address both body weight control and hepatic lipid accumulation simultaneously.

Pemvidutide TFA is an optimized dual incretin agonist, specifically designed to achieve:

• GLP-1R mediated glycemic control and appetite suppression

• GCGR mediated lipid mobilization and thermogenesis

This combination is thought to provide synergistic weight loss and liver fat reduction while maintaining metabolic stability.

Research Value

Studies suggest that Pemvidutide achieves striking reductions in body weight, liver fat, and serum triglycerides. In clinical development programs, participants experienced not only reduced adiposity but also improvements in biomarkers of liver function, systemic insulin sensitivity, and lipid metabolism.

As a TFA salt, Pemvidutide exhibits superior solubility and stability compared to its free form, making it easier to handle in experimental settings. This ensures reproducibility and consistency across laboratory models.

Application Areas

1. Obesity Research – Appetite suppression, increased satiety, weight reduction.

2. NASH Research – Reduction of hepatic fat, improved fibrosis biomarkers, decreased inflammation.

3. Metabolic Disorders – Regulation of insulin sensitivity, lipid metabolism, and glucose homeostasis.

4. Cardiometabolic Disease – Potential impact on atherosclerosis and dyslipidemia.

Product Specifications

Extended Technical Notes

• Peptide Backbone: The molecule is chemically optimized for receptor binding affinity and resistance to enzymatic degradation.

• Salt Form Advantage: The TFA salt improves aqueous solubility, enabling accurate dose-response assessments in preclinical studies.

• Quality Control: Each batch undergoes rigorous HPLC and mass spectrometry validation to ensure reproducibility.

• Storage Stability: Stability testing confirms reliable activity after long-term frozen storage.

• Laboratory Applications: Suitable for cell-based assays, in vivo metabolic studies, and comparative incretin research.

Mechanism of Action

Pemvidutide TFA exerts its effects by simultaneously activating GLP-1R and GCGR. This dual agonism leads to complementary metabolic outcomes.

GLP-1R Signaling

Activation of GLP-1R promotes:

• Insulin secretion in a glucose-dependent manner.

• Suppression of glucagon secretion under hyperglycemia.

• Delayed gastric emptying, leading to prolonged satiety.

• Appetite regulation through central nervous system pathways (hypothalamus).

GCGR Signaling

Activation of GCGR contributes to:

• Increased hepatic lipid oxidation, reducing intrahepatic fat.

• Energy expenditure via enhanced thermogenesis.

• Mobilization of stored triglycerides, improving systemic lipid profiles.

Dual Synergy

Unlike single agonists, Pemvidutide achieves:

• Enhanced weight loss through appetite suppression (GLP-1R) + fat burning (GCGR).

• NASH benefit by directly reducing liver fat while preventing further accumulation.

• Improved cardiovascular risk factors, including lipid modulation and insulin sensitivity.

Comparative Mechanistic Insights

• Compared with semaglutide (GLP-1 agonist only): Pemvidutide shows greater impact on hepatic steatosis.

• Compared with pure glucagon agonists: Pemvidutide avoids excessive hyperglycemia by maintaining GLP-1 mediated insulin control.

• This balance suggests that dual agonists may represent the next generation of incretin-based therapies.

  

Side Effects

While Pemvidutide TFA is promising, potential research-observed adverse effects must be considered:

Gastrointestinal Effects

• Nausea, vomiting, and diarrhea are common in incretin-based peptides.

• Dose titration in preclinical studies reduces GI-related dropout.

Metabolic Considerations

• Hyperglycemia risk: GCGR activation can raise fasting glucose, but balanced by GLP-1 insulinotropic effect.

• Hypoglycemia is rare due to glucose-dependent insulin secretion.

Hepatic and Pancreatic Safety

• Animal models show improved hepatic profiles, but long-term safety requires monitoring of liver enzymes.

• GLP-1 based compounds have raised questions regarding pancreatic safety; careful dose-dependent analysis is advised.

Cardiovascular Outcomes

• GLP-1 agonists are generally cardioprotective; however, dual agonism warrants careful study of blood pressure and heart rate variability.

Laboratory Handling Risks

• Like all peptides, handling should be done with protective gloves, lab coats, and sterile equipment.

• Product is for research use only, not suitable for diagnostic or therapeutic application.

Disclaimer

Pemvidutide TFA is supplied for laboratory research use only. Not approved for human consumption, diagnostic use, or therapeutic application.

Keywords

Pemvidutide TFA, ALT-801 peptide, dual GLP-1R GCGR agonist, obesity research compound, NASH peptide research, incretin-based therapy, liver fat reduction peptide, metabolic disorder peptide.

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