Squalamine

Squalamine

Names
IUPAC name (1S,2S,5S,7R,9R,10R,11S,14R,15R)-N-{3-[(4- aminobutyl)amino]propyl}-9-hydroxy-2,15-dimethyl- 14-[(2R,5R)-6-methyl-5-(sulfooxy)heptan-2- yl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-5- aminium
Identifiers
3D model (Jmol)	Interactive image
ChemSpider	65407
PubChem CID	72495
UNII	F8PO54Z4V7 Y
InChI InChI=1S/C34H65N3O5S/c1-23(2)31(42-43(39,40)41)12-9-24(3)27-10-11-28-32-29(14-16-34(27,28)5)33(4)15-13-26(21-25(33)22-30(32)38)37-20-8-19-36-18-7-6-17-35/h23-32,36-38H,6-22,35H2,1-5H3,(H,39,40,41)/t24-,25-,26+,27-,28+,29+,30-,31-,32+,33+,34-/m1/s1 Key: UIRKNQLZZXALBI-MSVGPLKSSA-N InChI=1/C34H65N3O5S/c1-23(2)31(42-43(39,40)41)12-9-24(3)27-10-11-28-32-29(14-16-34(27,28)5)33(4)15-13-26(21-25(33)22-30(32)38)37-20-8-19-36-18-7-6-17-35/h23-32,36-38H,6-22,35H2,1-5H3,(H,39,40,41)/t24-,25-,26+,27-,28+,29+,30-,31-,32+,33+,34-/m1/s1 Key: UIRKNQLZZXALBI-MSVGPLKSBB
SMILES CC(C)[C@@H](CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@H]4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)NCCCNCCCCN)OS(=O)(=O)O
Properties
Chemical formula	C34H65N3O5S
Molar mass	628 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Not to be confused with the similar-sounding squalene, an unrelated compound also found in shark liver.

Squalamine (/ˈskweɪləmiːn/ SKWAY-lə-meen) is an aminosterol compound with potent broad spectrum antimicrobial activity discovered in the tissues of the dogfish shark (Squalus acanthias) by a team led by Michael Zasloff. Dr. Zasloff searched the tissues of the dogfish for compounds that might help explain the hardiness of this animal to infection, despite its "primitive" immune system. Using techniques that Zasloff's team had developed to isolate and identify antimicrobial peptides from animal tissues, the team extracted and characterized a novel bile acid-like compound containing a polyamine never before seen in nature. The compound was called "squalamine", based on its source (Squalus acanthias) and its chemical structure (a sterol linked to a polyamine). Further analyses of larger quantities of dogfish liver extracts revealed squalamine to be the most abundant member of a larger aminosterol family comprising at least 12 related compounds. One of these, "MSI-1436" or trodusquemine, although structurally similar to squalamine (it carries a spermine rather than a spermidine) and also quite potent as an anti-infective, exhibits a profoundly different pharmacology in vertebrates, causing weight loss and adipose tissue mobilization.

Squalamine was initially discovered on the basis of its anti-bacterial activity. It has proven to be a broad spectrum antimicrobial compound that exhibits potent activity in vitro and in vivo against gram negative and gram positive bacteria,fungi, protozoa, and many viruses. Subsequent studies in vitro and in animals demonstrated various unanticipated pharmacological properties. In several vertebrate models, squalamine exhibits systemic anti-angiogenic activity against rapidly proliferating blood vessels that arise in pathological settings. As a consequence it is being evaluated in several human clinical trials for cancer, macular degeneration, diabetic retinopathy, and fibrodysplasia ossificans progressiva. Ohr Pharmaceuticals is currently evaluating squalamine in a Phase II study for angiopathic retinopathy applied topically to the eye. In mammals, systemically administered squalamine is cleared by the liver, and transported via the biliary system into the feces. Squalamine has been evaluated in trials for treatment of non-small cell lung cancer (stage I/IIA), ovarian cancer (stage IV), and prostate cancer as well as several phase I pharmacokinetic studies. In 2005, the Food and Drug Administration granted squalamine Fast Track status for approval for treatment of age-related macular degeneration.