Heparastatin is an inhibitor of heparanase, an enzyme that cleaves heparan sulfate into glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc).1 It inhibits heparanase in A375-M human melanoma cells expressing the recombinant human enzyme (IC50 = 10.55 ?M). Heparastatin also inhibits bovine liver β-glucuronidase and almond β-glucosidase (IC50s = 0.31 and 11 ?M, respectively). It reduces air pouch neutrophil and monocyte infiltration and levels of chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of dorsal air pouch inflammation induced by carrageenan.2 Heparastatin (100 mg/kg once per day) inhibits metastasis by 57.1% in a murine Lewis lung carcinoma model.3
1.Nishimura, Y., Shitara, E., Adachi, H., et al.Flexible synthesis and biological activity of uronic acid-type gem-diamine 1-N-iminosugars: A new family of glycosidase inhibitorsJ. Org. Chem.65(1)2-11(2000) 2.Sue, M., Higashi, N., Shida, H., et al.An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouchesInt. Immunopharmacol.3515-21(2016) 3.Nishimura, Y., Satoh, T., Kondo, S., et al.Effect on spontaneous metastasis of mouse Lewis lung carcinoma by a trifluoroacetamide analogue of siastatin BJ. Antibiot. (Tokyo)47(7)840-842(1994)