Journal of medicinal chemistry, 2003-07, Vol.46 (14), p.2973-2984
2003
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Details
- Autor(en) / Beteiligte
- Titel
- Dual Protein Farnesyltransferase−Geranylgeranyltransferase-I Inhibitors as Potential Cancer Chemotherapeutic Agents
- Ist Teil von
- Journal of medicinal chemistry, 2003-07, Vol.46 (14), p.2973-2984
- Ort / Verlag
- Washington, DC: American Chemical Society
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2623eISSN: 1520-4804DOI: 10.1021/jm020587nTitel-ID: cdi_proquest_miscellaneous_73395776
- Format
- –
- Schlagworte
- Alkyl and Aryl Transferases - antagonists & inhibitors, Animals, Antineoplastic agents, Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - chemistry, Antineoplastic Agents - pharmacology, Biological and medical sciences, Carrier Proteins - metabolism, Crystallography, X-Ray, Drug Screening Assays, Antitumor, General aspects, Heat-Shock Proteins - metabolism, HSP40 Heat-Shock Proteins, Humans, Medical sciences, Mice, Mice, Nude, Models, Molecular, Neoplasm Transplantation, Neoplasms, Experimental - drug therapy, Pharmacology. Drug treatments, Protein Prenylation, rap1 GTP-Binding Proteins - metabolism, ras Proteins - metabolism, Structure-Activity Relationship, Transplantation, Heterologous, Tumor Cells, Cultured