HPSE and cancer: Coupling the sulfated oligosaccharide to a lipophilic cholestanol aglycone significantly increased the elimination half-life in vivo, while reducing the unwanted anticoagulant activity associated with similar compounds [2] but retaining the potent inhibition of the heparan sulfate (HS)-degrading enzyme heparanase-1 (HPSE), a key drug target [1, 3, 4] considered a master regulator of the aggressive cancer phenotype [5–8].