Squalamine is a

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

polyamine A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...

conjugate compound with broad spectrum antimicrobial activity and anti-angiogenic activity. It was studied as a potential cancer drug and as a potential treatment for wet

macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...

but as of 2018 had not succeeded in Phase III trials for any use.

Pharmacology

Squalamine disrupts microbial membranes; the exact mechanism is not known. Squalamine appears to have an anti-angiogenic effect in mammalian cells by binding to

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...

once it is taken up by the cell; this prevents

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

downstream of pro-angiogenic factors like

VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...

Chemistry

Squalamine is a

conjugate. It was first isolated from the liver of

sharks Sharks are a group of elasmobranch fish characterized by a cartilaginous skeleton, five to seven gill slits on the sides of the head, and pectoral fins that are not fused to the head. Modern sharks are classified within the clade Selachimorp ...

of the genus ''

Squalus ''Squalus'' is a genus of dogfish sharks in the family Squalidae. Commonly known as spurdogs, these sharks are characterized by smooth dorsal fin spines, teeth in upper and lower jaws similar in size, caudal peduncle with lateral keels; upper ...

'' but methods to make it synthetically have been subsequently developed.

Research

Squalamine was studied as a potential drug to treat several forms of cancer and wet

by scientists at Magainin Pharmaceuticals (subsequently called Genaera), but the company ran out of money and closed in 2009. Squalamine and some other drug assets were sold to Ohr Pharmaceutical for $200,000 by Genaera's liquidator. It was studied in an eye drop formulation as a potential way to treat wet macular degeneration in combination with

ranibizumab Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment ( Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related m ...

by Ohr Pharmaceuticals. A Phase II trial failed in 2015, but Ohr said a subpopulation with choroidal neovascularization responded well enough to justify a Phase III trial. Ohr announced that the Phase III trial had failed in January 2018.

References

{{reflist Angiogenesis inhibitors Cholestanes Polyamines Antiviral drugs Secondary alcohols Secondary amines Sulfate esters