Effect of Squalamine on Iris Neovascularization in Monkeys

Abstract

Intravitreally injected squalamine did not affect the development of iris neovascularization; however, systemic squalamine injection inhibited the development of iris neovascularization and caused partial regression of new vessels in a primate model.

A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity

“…1B), an antimicrobial aminosterol originally discovered in 1993 in the dogfish shark, Squalus acanthias (14). This small molecule, now prepared synthetically (see SI Materials and Methods for details), has been found to have pharmacological activity in endothelial cells by inhibiting growth factor-dependent pathways and thus has emerged as a drug candidate for the treatment of cancer and macular degeneration (15,16). In the present context, our choice of studying squalamine was prompted by the observation that this molecule is able to enter eukaryotic cells and displace proteins that are bound to the cytoplasmic face of plasma membranes (17)(18)(19), suggesting that it may influence the initiation of the aggregation of α-synuclein (12).…”

Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential

“…Our hypothesis predicts that squalamine should interrupt this infection. At concentrations between 20 and 60 μg/mL, squalamine has been shown to inhibit a broad array of growth factor-induced, actin-dependent responses in endothelial cells, including cell migration, cell division, and vascular tube formation in a 3D matrix (4)(5)(6)(7)(8)(9)(10)(11).…”

“…1A) was first discovered in the tissues of the dogfish shark (Squalus acanthias) as a broad-spectrum antimicrobial agent in 1993 (1,2) and later identified within the circulating white blood cells of the sea lamprey (Petromyzon marinus) (3). It was found to have pharmacological activity in endothelial cells, inhibiting several growth factor-dependent processes (such as angiogenesis, migration, and proliferation) both in vitro and in vivo (4)(5)(6)(7)(8)(9)(10)(11). Recently, squalamine was discovered to enter cells and cause displacement of proteins that are associated through electrostatic interactions with the inner face of the cytoplasmic membrane (12)(13)(14).…”

Tratamento da forma neovascular de degeneração macular relacionada à idade com drogas antiangiogênicas

“…A injeção sistêmica do aminoesterol squalamina levou a inibição do surgimento de neovascularização na íris em um modelo experimental de neovascularização em macacos (54) . Em um modelo de retinopatia da prematuridade em camundongos, a injeção intraperitonial de squalamina na dose de 40 mg/kg bloqueou a neovascularização retiniana significativamente (55) .…”