1612221-29-0Relevant academic research and scientific papers
Dendrimer Heparan Sulfate Glycomimetics: Potent Heparanase Inhibitors for Anticancer Therapy
Zubkova, Olga V.,Ahmed, Yassir A.,Guimond, Scott E.,Noble, Sophia-Louise,Miller, John Holmes,Alfred Smith, Raymond Alexander,Nurcombe, Victor,Tyler, Peter C.,Weissmann, Marina,Vlodavsky, Israel,Turnbull, Jeremy E.
, p. 3236 - 3242 (2018)
Heparanase is a mammalian endoglycosidase that cleaves heparan sulfate (HS) polysaccharides and contributes to remodelling of the extracellular matrix and regulation of HS-binding protein bioavailabilities. Heparanase is upregulated in malignant cancers and inflammation, aiding cell migration and the release of signaling molecules. It is established as a highly druggable extracellular target for anticancer therapy, but current compounds have limitations, because of cost, production complexity, or off-target effects. Here, we report the synthesis of a novel, targeted library of single-entity glycomimetic clusters capped with simple sulfated saccharides. Several dendrimer HS glycomimetics display low nM IC50 potency for heparanase inhibition equivalent to comparator compounds in clinical development, and potently inhibit metastasis and growth of human myeloma tumor cells in a mouse xenograft model. Importantly, they lack anticoagulant activity and cytotoxicity, and also inhibit angiogenesis. They provide a new candidate class for anticancer and wider therapeutic applications, which could benefit from targeted heparanase inhibition.
HEPARAN SULFATE GLYCOMIMETIC COMPOUNDS AND THEIR PHARMACEUTICAL AND COSMECEUTICAL USES
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Page/Page column 39, (2018/10/19)
The invention relates to dendritic compounds, the use of these compounds as pharmaceuticals, pharmaceutical and cosmeceutical compositions containing the compounds, and methods of treating cancer, inflammation, diabetic nephropathy, neurodegenerative disorders, Niemann-Pick Type C disease, or dermatological conditions.
DENDRITIC CORE COMPOUNDS
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Page/Page column 47, (2014/06/23)
The invention relates to compounds that are useful for the preparation of dendrimer compounds, the use of these compounds for preparing dendrimers and processes for preparing the compounds.
