Merck + Co., Inc.

Denis R Patrick

Hans E Huber

Deborah L Zink

Otto D Hensens

Gerald F Bills

Seok H Lee

Fernando Pelaez

Leeyuan Huang

Anne W Dombrowski

Maria T Diez

David C Heimbrook

Stanley F Barnett

Rosalind G Jenkins

M Dolores Vilella Amils

Marina Mojena Sanchez

Annie Z Zhao

The instant invention provides for a method of inhibiting prenyl-protein transferases and treating cancer which comprises administering to a mammal a prenyl-protein transferase inhibitor which is efficacious in vivo as an inhibitor of geranylgeranyl-protein transferase type I (GGTase-I). The invention also provides for a method of inhibiting farnesyl-protein transferase and geranylgeranyl-protein transferase type I by administering a compound that is a dual inhibitor of both of those prenyl-protein transferases. The invention also provides for a method of identifying such a compound, the method comprising a modified inhibitory assay that incorporates a modulator anion that alters the in vitro potency of prenyl-protein transferase inhibitors in a way that predicts their potency in vivo, thus providing convenient identification of compounds that possess such in vivo activity.

Method of treating cancer

A compound represented by the formula I is disclosed: ##STR1## or a pharmaceutically acceptable salt or hydrate thereof. The compound has inhibitory activity against the oncoprotein Raf. Also included are pharmaceutical compositions, methods of treating cancer, cultures of the producing fungal microorganism and methods of fermentative production of the compound.

Bis-aryl ethers, compositions containing such compounds and methods of

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Chalfont, PA, United States of America

Denis R Patrick