Adipotide 10mg

What is Adipotide?

Adipotide is a peptide drug candidate currently in clinical trials, also known as prohibitin-tp 01 or FTPP. It is a synthetic pro-apoptotic peptide that selectively targets the blood vessels supplying adipocytes. By severing the blood supply to fat cells, it induces apoptosis through hypoxia and nutrient deprivation, thereby facilitating weight loss.

Adipotide Structure

Source: PubChem

Sequence: CKGGRAKDCGGKLAKLAKKLAKLAK

Molecular Formula: C111H206N36O28S2

Molecular Weight: 2557.2 g/mol

CAS Number: 859216-15-2

PubChem CID：163360068

Synonyms: HKPao

Adipotide Research

What is the research background of Adipotide?

Globally, obesity has become an increasingly severe problem. Epidemiological studies from 2008 indicate that as many as 33.9% of adults in the United States suffer from obesity. Obesity is not merely about weight gain; it is closely linked to numerous serious health issues, including hypertension, hyperlipidemia, metabolic syndrome, non-insulin-dependent metabolism, cerebrovascular accidents, myocardial infarction, and various cancers. Additionally, abdominal fat poses greater health risks than fat in the lower limbs or buttocks due to its higher lipolysis activity.

Initially developed as a cancer treatment agent, Adipotide aimed to cut off blood supply to cancer cells, starving them of nutrients and halting their growth. Researchers serendipitously discovered that when this drug acts on fat cells in the bloodstream, it similarly starves them, forcing fat cells to die and be reabsorbed by the body. Researchers hope Adipotide's unique mechanism will offer new treatment options for obese individuals.

How does Adipotide work?

Inducing apoptosis in white adipose tissue vascular cells

Targeted action: Adipotide specifically targets blood vessels within white adipose tissue. It precisely locates and acts on vessels surrounding white fat deposits. Barnhart K F et al. demonstrated that this targeting allows Adipotide to act directly on white adipose tissue vessels without broadly affecting the vascular system in other body regions[1,2,3].

Triggering Apoptosis: When adipotide binds to adipose tissue blood vessels, it induces apoptosis in the cells within these vessels. Apoptosis is a programmed cell death process that is essential for maintaining normal tissue structure and function under physiological conditions. However, the apoptosis induced by adipotide is specifically targeted to adipose tissue blood vessels. Following apoptosis of adipose tissue vascular cells, vascular integrity is compromised, leading to reduced blood supply to adipose tissue. This effectively severs the “nutrient delivery pipeline” to adipose tissue, depriving adipocytes of sufficient nutrients and oxygen. Consequently, adipocytes cannot sustain normal metabolism and growth, ultimately undergoing death or atrophy, thereby achieving adipose tissue reduction[3,5].

Fig. 1 Anthropometric assessment of four obese rhesus monkeys treated with increasing doses of adipotide (0.10, 0.25, 0.43, and 0.75 mg/kg)[3].

Leading to weight loss

Fat tissue reduction: Adipotide induces apoptosis in adipose tissue vessels, causing gradual reduction of white adipose tissue due to ischemia and hypoxia. White adipose tissue serves as the primary site for fat storage in the human body. Its substantial reduction directly resulted in weight loss. In experiments involving obese monkeys, imaging techniques such as magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) confirmed that adipotide-treated obese monkeys exhibited a marked decrease in white adipose tissue, leading to rapid weight reduction. This process represents genuine depletion of fat reserves—not mere water loss or muscle wasting—providing a robust physiological basis for weight reduction [4,5].

What are the applications of Adipotide?

Obesity Treatment

Induction of Adipose Tissue Vascular Apoptosis: Studies in obese Old World monkeys revealed that Adipotide induces targeted apoptosis within the vascular system of white adipose tissue. White adipose tissue plays a critical role in energy storage and metabolic regulation, and excessive accumulation of white fat is a major contributor to obesity. By promoting apoptosis in white adipose tissue vessels, Adipotide disrupts the blood supply to fat tissue, causing fat cells to undergo apoptosis due to insufficient nutrient supply. This achieves the goal of reducing white adipose tissue and promoting weight loss. In Barnhart K F's study, obese monkeys treated with Adipotide experienced rapid weight loss, demonstrating its significant efficacy in obesity treatment [3].

Improving Insulin Resistance: Obesity is often accompanied by insulin resistance. Adipotide not only reduces body weight but also improves insulin resistance. Insulin resistance refers to a state where target organs exhibit reduced sensitivity to insulin's effects, meaning normal insulin doses produce suboptimal biological responses. This leads to elevated blood glucose levels and triggers a series of metabolic disorders. The mechanism by which Adipotide improves insulin resistance may involve reducing white adipose tissue, improving adipokine secretion, and regulating insulin signaling pathways. In Barnhart K F's study on obese monkeys, insulin resistance improved following Adipotide administration [3].

As a Prototype for Obesity Therapeutics: Due to biological differences between rodents and primates, translating anti-obesity strategies discovered or developed in rodents into effective human therapies faces significant hurdles. Adipotide's success in primate studies (e.g., obese monkeys) positions it as a prototype for a novel class of therapeutic candidates [3].

Conclusion

As a ligand-directed peptidomimetic, Adipotide demonstrates distinct effects in primate studies: it specifically induces apoptosis in white adipose tissue vasculature, reduces fat accumulation to achieve weight loss, and improves obesity-related insulin resistance, thereby offering therapeutic potential for obesity treatment.

About The Author

The above-mentioned materials are all researched, edited and compiled by Corevia Peptides.

Scientific Journal Author

Kirstin F. Barnhart is a researcher specializing in molecular pharmacology and drug development. She has co-authored studies focusing on the design and evaluation of peptidomimetic compounds for therapeutic applications. Her work contributes to the advancement of targeted drug delivery systems and the understanding of their effects in preclinical models. Kirstin F. Barnhart is listed in the reference of citation [3].

Relevant Citations

[1] Christianson D, Kolonin M, Hulvat J, Chan L, Arap W, Pasqualini R. Response to Comment on "A Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance in Obese Monkeys". Science Translational Medicine 2012; 4: 131lr2.DOI: 10.1126/scitranslmed.3004103.

[2] Fiaschi T. Mechanisms of Adiponectin Action. International Journal of Molecular Sciences 2019; 20(12).DOI: 10.3390/ijms20122894.

[3] Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin  resistance in obese monkeys. Science Translational Medicine 2011; 3(108): 108ra112.DOI: 10.1126/scitranslmed.3002621.

[4] Lalumiere R, Kalivas P. Cocaine addiction: Mechanisms of action. Psychiatric Annals 2008; 38: 252-258.

[5] Criscione L. Comment on "a peptidomimetic targeting white fat causes weight loss and improved  insulin resistance in obese monkeys". Science Translational Medicine 2012; 4(131): 131le2, 131l-132l.DOI: 10.1126/scitranslmed.3003760.