title: Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery, biology and clinical observations.
abstract: Farnesyl Protein Transferase as a target for therapeutic intervention is currently under investigation in human clinical trials. Sch-66336 (sarasar), a benzocycloheptapyridyl Farnesyl Transferase Inhibitor (FTI), has been found to be effective in cellular proliferation assays and in in vivo oncology models both as a single agent and in combination with other anti-cancer agents. Clinically, early evidence is being generated that suggests efficacy in humans, particularly in patients with leukemia. Herein, we review the biology of FPT, the discovery of Sch-66336 and other benzocycloheptapyridyl FTIs, and the clinical evaluation of Sch-66336 for the treatment of leukemia and solid tumors.
authors.affiliation: Department of Medicinal Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. arthur.taveras@spcorp.com
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Taveras
authors.forename: Paul
authors.initials: P
authors.lastname: Kirschmeier
authors.forename: Charles M
authors.initials: CM
authors.lastname: Baum
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000628:therapy*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D003986:Dibenzocycloheptenes
chemical_list: D019883:Alkyl and Aryl Transferases; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D010880:Piperidines; D011725:Pyridines; C115354:lonafarnib; D003986:Dibenzocycloheptenes