Adipotide 5mg

Compound Name: Adipotide

Synonyms: CKGGRAKDC-GG-D(KLAKLAK)₂, Prohibitin-targeting proapoptotic peptide, 859216-15-2, HKPao, EX-A6186, DA-74204

CAS Number: 859216-15-2

Molecular Formula: C₁₁₁H₂₀₆N₃₆O₂₈S₂

Molecular Weight: ~2557.2 g/mol

Structure: Disulfide-bridged cyclic peptide (CKGGRAKDC) linked via glycine-glycine to a proteolysis-resistant amphipathic D-enantiomeric proapoptotic motif D(KLAKLAK)₂

Peptide Sequence: H-Cys-Lys-Gly-Gly-Arg-Ala-Lys-Asp-Cys-Gly-Gly-D-Lys-D-Leu-D-Ala-D-Lys-D-Leu-D-Ala-D-Lys-D-Lys-D-Leu-D-Ala-D-Lys-D-Leu-D-Ala-D-Lys-OH

Chemical Structure:

Source: PubChem

Mechanism of Action: Adipotide functions by selectively targeting the prohibitin receptor on endothelial cells within white adipose tissue vasculature via its CKGGRAKDC motif. Upon binding, the conjugated D(KLAKLAK)₂ domain is internalized into the cells, where it disrupts mitochondrial membranes, triggering targeted apoptosis of the vasculature. This results in a collapse of blood supply to white adipose tissue, leading to fat resorption and reduction in adipose mass without affecting other tissues or relying on central appetite regulation pathways^1-4.

Biological Activity: In vivo studies demonstrate that Adipotide induces pronounced and rapid weight loss in rodent and primate models of obesity by selectively ablating the vasculature of white fat. This effect reduces total body fat, improves insulin sensitivity, decreases serum leptin, and reverses diet-induced or genetic obesity, all with a generally reversible and predictable renal side effect profile and no evidence of visceral illness or malabsorption^1-4.

Storage: Store at –20°C, protected from light. Reconstituted solution should be aliquoted and stored at –20°C and used within 2 weeks.

Drug Categories: Experimental anti-obesity agent, Peptidomimetic, Angiogenesis inhibitor

Additional Notes:

• Not approved for clinical use in humans; for research purposes only.
• Designed for maximized selectivity to white adipose vasculature.

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

Preclinical studies in rodent and nonhuman primate models have shown that Adipotide administration results in striking weight loss, robust reduction of visceral and subcutaneous adipose tissue, and significant improvements in insulin resistance—all without the adverse neuropsychiatric or gastrointestinal effects that limit current obesity drugs. The compound’s effects are obesity-specific in primates: lean animals show minimal response, highlighting specificity for pathological adipose tissue. Renal toxicity, characterized by reversible tubular injury, is the main dose-limiting side effect observed in primate studies; other metabolic parameters such as lipid profiles remain stable during treatment

Research Highlights

• Selectively targets adipose endothelial cells via prohibitin-binding CKGGRAKDC motif¹.
• Delivers proapoptotic D(KLAKLAK)₂ peptide, disrupting mitochondrial function and triggering apoptosis².
• Induces rapid, significant weight and fat loss in rodent and primate obesity models, with average reductions of 30–40% body fat³.
• Improves insulin sensitivity and reduces serum insulin and leptin levels, with no detectable adverse effects on engagement of appetite or malabsorption⁴.

Mechanism of Action

Prohibitin Receptor Binding (CKGGRAKDC motif)

• Highly specific binding to prohibitin expressed on the surface of endothelial cells in white adipose tissue, allowing selective targeting and internalization of the linked peptide cargo¹.

Mitochondria-Targeted Apoptosis [D(KLAKLAK)₂ domain]

• After binding and uptake, the D(KLAKLAK)₂ sequence disrupts mitochondrial membranes, activating intrinsic apoptotic cascades and specifically inducing death of the adipose endothelial cell, leading to regression of the supporting vasculature and resorption of fat^2-4.

Physiological/Systemic Outcomes

• Fat loss is achieved through degeneration of the white fat blood supply, resulting in reduced adiposity, decreased insulin resistance, and improved metabolic profiles¹.
• Minimal to no effect on CNS appetite-regulation circuits, preserving food intake regulatory feedback and limiting off-target adverse effects².
• Effect selective for obese (not lean) animals in primate models⁴.

Pharmacokinetic Profile:

• Route of Administration: Subcutaneous injection (in animal models)
• Dosing Frequency: Daily, but duration depends on study design
• Half-Life: Not formally established in humans

Formulation & Handling

• Lyophilized powder, reconstitute with sterile buffer
• Use within indicated stability window after reconstitution
• Protect from light, store at –20°C

Selected Clinical Trial Activity

Adipotide is a research-grade compound that has been studied in laboratory settings but has not undergone full clinical development. It is not approved for therapeutic use in humans, and no large-scale clinical trials have been conducted to evaluate its safety or efficacy as a medication. Adipotide is supplied strictly for laboratory research and investigational purposes only.

References

¹Kolonin, M.G., Saha, P.K., Chan, L., Pasqualini, R. & Arap, W. Reversal of obesity by targeted ablation of adipose tissue. Nat. Med. 10, 625–632 (2004).

²Barnhart, K.F. et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci. Transl. Med. 3, 108ra112 (2011).

³Kim, D.H. et al. Attenuation of obesity by an adipocyte-targeting peptide in mice and monkeys. Diabetes 59, 907–915 (2010).

⁴Arap, W., Kolonin, M.G., Trepel, M., Lahdenranta, J., Cardó-Vila, M., Giordano, R.J. et al. Steps toward mapping the human vasculature by phage display. Nat. Med. 8, 121–127 (2002).