| Literature DB >> 12825937 |
S Jane deSolms1, Terrence M Ciccarone, Suzanne C MacTough, Anthony W Shaw, Carolyn A Buser, Michelle Ellis-Hutchings, Christine Fernandes, Kelly A Hamilton, Hans E Huber, Nancy E Kohl, Robert B Lobell, Ronald G Robinson, Nancy N Tsou, Eileen S Walsh, Samuel L Graham, Lorena S Beese, Jeffrey S Taylor.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2003 PMID： 12825937 DOI： 10.1021/jm020587n
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446