Dual Protein Farnesyltransferase−Geranylgeranyltransferase-I Inhibitors as Potential Cancer Chemotherapeutic Agents

Autor:	Terrence M. Ciccarone, Hans E. Huber, Samuel L. Graham, Ronald G. Robinson, Jeffrey S. Taylor, Lorena S. Beese, Michelle Ellis-Hutchings, Robert B. Lobell, Nancy E. Kohl, Anthony W. Shaw, Eileen S. Walsh, Nancy N. Tsou, Desolms S Jane, Christine Fernandes, Suzanne C. Mactough, Kelly Hamilton, Carolyn A. Buser
Rok vydání:	2003
Předmět:	Models Molecular Farnesyltransferase Transplantation Heterologous Protein Prenylation Mice Nude Antineoplastic Agents Crystallography X-Ray Mice Structure-Activity Relationship Prenylation Drug Discovery Tumor Cells Cultured Animals Humans Structure–activity relationship Heat-Shock Proteins chemistry.chemical_classification Farnesyl-diphosphate farnesyltransferase Alkyl and Aryl Transferases biology Oncogene Chemistry rap1 GTP-Binding Proteins Neoplasms Experimental HSP40 Heat-Shock Proteins Enzyme Biochemistry Enzyme inhibitor ras Proteins biology.protein Molecular Medicine Protein prenylation Drug Screening Assays Antitumor Carrier Proteins Neoplasm Transplantation
Zdroj:	Journal of Medicinal Chemistry. 46:2973-2984
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm020587n
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7157b39100cc527794d744d80896dbd https://doi.org/10.1021/jm020587n Zobrazit plný text záznamu