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

Publication ,  Journal Article
deSolms, SJ; Ciccarone, TM; MacTough, SC; Shaw, AW; Buser, CA; Ellis-Hutchings, M; Fernandes, C; Hamilton, KA; Huber, HE; Kohl, NE; Lobell, RB ...
Published in: J Med Chem
July 3, 2003

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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Published In

J Med Chem

DOI

ISSN

0022-2623

Publication Date

July 3, 2003

Volume

46

Issue

14

Start / End Page

2973 / 2984

Location

United States

Related Subject Headings

  • ras Proteins
  • rap1 GTP-Binding Proteins
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Structure-Activity Relationship
  • Protein Prenylation
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Models, Molecular
  • Mice, Nude
 

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deSolms, S. J., Ciccarone, T. M., MacTough, S. C., Shaw, A. W., Buser, C. A., Ellis-Hutchings, M., … Taylor, J. S. (2003). Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. J Med Chem, 46(14), 2973–2984. https://doi.org/10.1021/jm020587n
deSolms, S Jane, Terrence M. Ciccarone, Suzanne C. MacTough, Anthony W. Shaw, Carolyn A. Buser, Michelle Ellis-Hutchings, Christine Fernandes, et al. “Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.J Med Chem 46, no. 14 (July 3, 2003): 2973–84. https://doi.org/10.1021/jm020587n.
deSolms SJ, Ciccarone TM, MacTough SC, Shaw AW, Buser CA, Ellis-Hutchings M, et al. Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. J Med Chem. 2003 Jul 3;46(14):2973–84.
deSolms, S. Jane, et al. “Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.J Med Chem, vol. 46, no. 14, July 2003, pp. 2973–84. Pubmed, doi:10.1021/jm020587n.
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. Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. J Med Chem. 2003 Jul 3;46(14):2973–2984.
Journal cover image

Published In

J Med Chem

DOI

ISSN

0022-2623

Publication Date

July 3, 2003

Volume

46

Issue

14

Start / End Page

2973 / 2984

Location

United States

Related Subject Headings

  • ras Proteins
  • rap1 GTP-Binding Proteins
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Structure-Activity Relationship
  • Protein Prenylation
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Models, Molecular
  • Mice, Nude