Metabolic
A synthetic peptidomimetic studied for selective targeting of white adipose tissue vasculature.
Adipotide is a synthetic peptidomimetic investigated for its ability to home to blood vessels in white adipose tissue. Researchers examine it in preclinical models to study its binding to adipose endothelium and the apoptotic processes observed in those cells. It consists of a vascular-homing segment (CKGGRAKDC) linked to a proapoptotic helical domain (D(KLAKLAK)₂), designed to associate with a receptor on adipose tissue blood vessels.
Type
Synthetic peptide (peptidomimetic)
Molecular formula
C₁₁₁H₂₀₆N₃₆O₂₈S₂
Molecular weight
2557.2 g/mol
CAS number
859216-15-2
Amino acids
26
Sequence
CKGGRAKDC-GG-D(KLAKLAK)₂
Modification
Contains two D-enantiomeric (D-amino acid) heptapeptide repeats forming an amphipathic proapoptotic domain; cysteine residues present in the homing motif; linear conjugate connected by a GG linker.
Adipotide is a ligand-directed vascular-targeting peptidomimetic. The CKGGRAKDC homing segment binds to prohibitin (PHB), a protein enriched on the surface of endothelial cells in white adipose tissue. Biochemical studies have examined whether this sequence mimics an internal loop of annexin A2 (ANXA2), a PHB-associated protein co-expressed on adipose endothelial surfaces. The conjugated D(KLAKLAK)₂ proapoptotic domain is a membrane-disrupting helical peptide that, upon internalization, engages mitochondrial membranes and is studied for its role in initiating endothelial cell apoptosis. Separate research has examined the formation of a PHB–ANXA2–CD36 complex and its potential contribution to fatty acid transport at the adipose endothelium.
Research Focus
Studied in preclinical obesity models and in vitro systems examining adipose tissue vasculature, endothelial apoptosis, and prohibitin/annexin A2 receptor biology.
The Adipotide concept originated from in vivo phage display experiments designed to identify peptide sequences that selectively home to blood vessels of white adipose tissue. Kolonin et al. (2004) screened phage libraries in obese mice and isolated the CKGGRAKDC homing motif, identifying prohibitin (PHB) — a protein found on adipose endothelial cell surfaces — as its binding partner. The conjugate CKGGRAKDC-GG-D(KLAKLAK)₂ was assembled by linking this homing motif to a proapoptotic helical domain and studied for its vascular-targeting properties in the adipose context. Staquicini et al. (2011) applied combinatorial vascular receptor mapping to examine receptor expression — including PHB and annexin A2 — in human white adipose tissue.
Kim et al. (2010) studied Adipotide in diet-induced obese mice and rats over a multi-week administration period. The study monitored metabolic and neuroendocrine parameters across the treatment period. The research examined relationships between adipose vascular targeting and systemic signaling in the rodent obesity model context.
Barnhart et al. (2011) examined Adipotide in obese rhesus macaques in a 4-week dose-ranging study. Investigators tracked biodistribution and changes in adipose tissue parameters using adipose imaging, examining whether adipose vascular targeting and biodistribution behavior observed in rodent models is present in primate physiology. These non-human primate studies were carried out to develop the translational research context for the compound.
Salameh et al. (2016) investigated the PHB–annexin A2 (ANXA2) interaction at the adipose endothelial surface using in vitro and ex vivo models. The study examined co-expression of PHB and ANXA2 on white adipose tissue endothelial cells, and characterised the assembly of a PHB–ANXA2–CD36 complex in the context of fatty acid exposure, examining whether the complex plays a role in transendothelial lipid handling. Knockout mouse models lacking ANXA2 were studied to examine the pathway's contribution to adipose lipid handling. Separately, phage peptide sequence analysis examined alignment of the CKGGRAKDC motif with regions of ANXA2, providing structural context for the PHB-targeting interaction.
A Phase I open-label trial (NCT01262664) examined pharmacokinetic and safety parameters of Adipotide in human participants with metastatic prostate cancer and obesity. Detailed published data from this trial are not yet available.
Lyophilized
Store dry at −20 °C or below, protected from moisture and light.
Reconstituted
Dissolve in sterile water or dilute acetic acid
keep at 4 °C for short-term use; divide into aliquots prior to freezing and store at −80 °C.
Aliquot to avoid repeated freeze-thaw cycles; protect from light and heat.
Clinical
ClinicalTrials.gov (2012). ClinicalTrials.gov — Phase I open-label trial of Adipotide in patients with metastatic prostate cancer and obesity
Primary research
Salameh A., Daquinag A.C., Staquicini D.I., An Z., Hajjar K.A., Pasqualini R., Arap W., Kolonin M.G. (2016). JCI Insight — In vitro and ex vivo study of PHB–annexin A2 interaction and fatty acid transport in white adipose endothelium
Staquicini F.I., Cardó-Vila M., Kolonin M.G., Treplev M., et al. (2011). PNAS — Combinatorial vascular receptor mapping examining prohibitin and annexin A2 expression in human white adipose tissue
Primary research
Barnhart K.F., Christianson D.R., Wetterau L., Erickson J.A., et al. (2011). Sci Transl Med — Dose-ranging study of Adipotide in obese Old World monkeys examining biodistribution and adipose tissue parameters
Kim D.-H., Woods S.C., Seeley R.J. (2010). Diabetes — Study of Adipotide in diet-induced obese rodents monitoring metabolic and neuroendocrine parameters
Kolonin M.G., Saha P.K., Chan L., Pasqualini R., Arap W. (2004). Nat Med — Phage display identification of the CKGGRAKDC adipose-vascular homing motif and prohibitin as its receptor
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
