title: Current perspective of TACE inhibitors: a review.
abstract: Rheumatoid Arthritis (RA) is one of the most common autoimmune inflammatory conditions, affecting approximately 1% of the adult population worldwide. TNF-alpha is a pleitropic, pro-inflammatory cytokine which plays a pivotal role in the origin and progression of RA and other immune mediated disorders. The success of anti-TNF-alpha biological agents proved that inhibition of TNF-alpha could result in effective control of RA. Since the discovery of anti-TNF-alpha biologicals, much efforts have gone into developing an orally bioavailable small size TNF-alpha antagonist. One of the ways to block TNF-alpha in biological fluids is to inhibit TNF-alpha converting enzyme (TACE). This target has been validated in preclinical trials using TACE inhibitors. But, even after more than a decade no single TACE inhibitor has passed the Phase II clinical trials. Very recently, it has been shown that TACE inhibitors could also be used for inhibition of pathogenic EGFR signaling in cancer. Hence, TACE inhibitors could perform a dual role, in curing not only RA but also certain cancerous conditions. Developments in the field have prompted us to review the research work on TACE inhibitors, especially their structure activity relationships and molecular modeling studies.
authors.affiliation: Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara 390 001, Gujarat, India.
authors.forename: Shirshendu
authors.initials: S
authors.lastname: DasGupta
authors.forename: Prashant R
authors.initials: PR
authors.lastname: Murumkar
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*; D000072198:ADAM17 Protein; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human