Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.

Journal Article (Journal Article)

A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex formed between one of these compounds and FTase has been determined by X-ray crystallography. These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal.

Full Text

Duke Authors

Cited Authors

  • deSolms, SJ; Ciccarone, TM; MacTough, SC; Shaw, AW; Buser, CA; Ellis-Hutchings, M; Fernandes, C; Hamilton, KA; Huber, HE; Kohl, NE; Lobell, RB; Robinson, RG; Tsou, NN; Walsh, ES; Graham, SL; Beese, LS; Taylor, JS

Published Date

  • July 3, 2003

Published In

Volume / Issue

  • 46 / 14

Start / End Page

  • 2973 - 2984

PubMed ID

  • 12825937

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm020587n


  • eng

Conference Location

  • United States