Background

Because uncontrolled growth of blood vessels (angiogenesis) contributes to the progression of diverse diseases from cancer to macular degeneration, drugs targeting the neovasculature are obvious candidates to control unwanted vascularization and tumor growth. However, most anti-angiogenic drugs must be taken up into the target cell in order to exert their effects. The availability of a potent drug that tackles angiogenesis via a different mode presents  a valuable therapeutic strategy for diseases that depend on abnormal neovasculature.

Technology Description

University researchers have synthesized a novel lipopeptide, Somocystinamide A (ScA), which is a synthetic version of a compound isolated from marine cyanobacteria. ScA is distinguished by a lipophilic structure similar to native membrane components and this unique structure enables ScA to directly integrate into cellular membranes, perturb normal lipid homeostasis and selectively activate caspase 8, leading to programmed cell death.

Applications

The promise of anti-angiogenic drugs in is reflected in the plethora of clinical trials. The obvious applications are reflected in the distribution of ~3000 human anti-angiogenesis trials:

~85% are designed to treat various forms of cancer and

~10% are for macular degeneration and a other eye diseases (e.g., choroid & retinal diseases)

Advantages

Advantages of ScA include: 

• A bioactive lipopeptide that can directly integrate into lipophilic structures such as liposomes, thus acting a bioactive structural component. This does not require active uptake into the liposome interior, and leaves the interior free for other cargo. 
  
• Excellent potency, with an IC50 of 0.5pM against human endothelial cells and 80nM in zebra fish;
• Long, lipophilic hydrocarbon chains are readily formulated into liposomes, which can be further customized and or targeted.; and 
  
• Combination therapy whereby ScA melts into the liposomal bilayer and additional anti-cancer drug(s) can be loaded into the liposomal lumen.In sum, ScA's unique, lipophilic structure confers improved functionality and efficacy, which may greatly improve the therapeutic window over other, anti-angiogenic drugs.
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State Of Development

ScA has been incorporated into stable, liposomal nanoparticles of 100 nM in size, which retain full potency and excellent activity in vitro and in vivo. In vivo, ScA blocks endothelial cell tube formation and developmental angiogenesis in zebrafish models. 

ScA: 

Related Materials

• www.marinebiotech.org  — 05/11/2012
• Discovery of Natural Antiangiogenic Leads  — 05/11/2012
• Wrasidlo, W., et al., The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc Natl Acad Sci U S A, 2008. 105(7): p. 2313-8.  — 02/19/2008
• Suyama, T.L. and W.H. Gerwick, Stereospecific total synthesis of somocystinamide A. Org Lett, 2008. 10(20): p. 4449-52.  — 02/13/2008
• Nogle, L.M. and W.H. Gerwick, Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage. Org Lett, 2002. 4(7): p. 1095-8.  — 04/04/2002