University of Texas System

Genentech, Inc.

Guy L James

Joseph L Goldstein

Michael S Brown

Robert S McDowell

David A Oare

Mark E Reynolds

Thomas E Rawson

Todd C Somers

Craig W Crowley

James C Marsters

Disclosed are methods and compositions for the identification of inhibitors of farnesyltransferase enzymes involved in the prenylation of various cellular proteins, including cancer related ras proteins, such as p21.sup.ras, particularly, K-rasB. Enclosed are procedures for using purified farnesyltransferase enzymes and K-rasB proteins in screening protocols for the identification of possible anticancer agents that inhibit the enzyme and thereby prevent prenylation of proteins such as K-RasB.

Methods for the identification of farnesyltransferase inhibitors

Ras farnesyl transferase inhibitors

Benzodiazepine derivatives are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases for which inhibition of the ras farnesyl:protein transferase is indicated. Also disclosed are benzazepines of the following general formula (II) having similar utility as the aforementioned benzodiazepines: ##STR1##

Growing community of inventors

Dallas, TX, United States of America

Guy L James