期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 46, 期 14, 页码 2973-2984出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm020587n
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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.
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