title: Novel TACE inhibitors in drug discovery: a review of patented compounds.
abstract: TNF-alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-alpha from membrane bound TNF-alpha precursor protein. TNF-alpha is believed to play pathophysiological roles in inflammation, anorexia, cachexia, septic shock, viral replication and so on. TNF-alpha is a key player in inflammation and joint damage in rheumatoid arthritis. While a variety of TACE inhibitors have been reported in the literature, a vast majority of these compounds are peptidic and peptide-like compounds that are expected to have bioavailability and pharmacokinetic problems, common to such compounds, limiting their clinical effectiveness. Low molecular mass, long acting, orally bioavailable inhibitors of TACE are, therefore, highly desirable for the treatment of potential chronic diseases mentioned above. A review of patented compounds as TACE inhibitors in drug discovery is given. A selection of interesting patents recorded from 2001 to 2009 is presented. Various novel TACE inhibitors developed by different companies have been discussed.
authors.affiliation: The M.S. University of Baroda, Faculty of Technology & Engineering, Department of Pharmacy, Kalabhavan, Vadodara, 390 001, India.
authors.forename: Prashant R
authors.initials: PR
authors.lastname: Murumkar
authors.forename: Shirshendu
authors.initials: S
authors.lastname: DasGupta
authors.forename: Sneha R
authors.initials: SR
authors.lastname: Chandani
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072198:ADAM17 Protein; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D015195:Drug Design; D004345:Drug Industry; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D010330:Patents as Topic
chemical_list: D004791:Enzyme Inhibitors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human