title: Sulfatase inhibitors: a patent review.
abstract: BACKGROUND
  Steroid sulfatase (STS) converts sulfated hormones to free hormones of importance in hormone-dependent diseases such as breast cancer and endometriosis. Carbohydrate sulfatases degrade complex carbohydrates as part of normal cellular turnover; certain lysosomal storage disorders (LSDs) involve defective processing of sulfated glycosaminoglycans by mutant sulfatases.
  
  
  METHODS
  Aryl sulfamates have been developed as STS inhibitors, and STX64 and PGL2001 are under evaluation in Phase I and II clinical trials for treatment of endometrial and metastatic breast and prostate cancers and endometriosis. Dual-acting compounds have emerged that are aromatase inhibitors (AIs), selective estrogen receptor antagonists, or inhibitors of microtubule polymerization. Sulfamidase inhibitors as pharmacological chaperones to assist maturation of folding-defective mutants for the treatment of Sanfilippo type A disease are under investigation. Coverage: The patent literature after the mid-1990s.
  
  
  CONCLUSIONS
  The failure of STX64 in a Phase II monotherapy clinical trial should not dissuade further investigations in multidrug regimens, particularly in combination with AIs. The recent development of dual-acting compounds may enhance the potential for success in the clinic. Further investigations into aryl sulfamates are required to clarify the molecular mechanism of action; additionally, new reversible sulfatase inhibition concepts are needed for the development of pharmacological chaperones for sulfatase LSDs.
authors.affiliation: University of Melbourne, School of Chemistry and Bio21 Molecular Science, Parkville, Victoria, Australia. sjwill@unimelb.edu.au
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D009084:Mucopolysaccharidosis III / Q000188:drug therapy / Q000473:pathology; D010330:Patents as Topic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; C560930:estradiol-3-O-sulfamate; C520511:irosustat; D004958:Estradiol; D043266:Steryl-Sulfatase