Inhibitors of farnesyltransferase

Details Inhibitors of farnesyltransferase Inhibitors of farnesyltransferase

1995-05-30

1998-11-10

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

562545, 562557, 562559, A61K 3805

Patent

active

058344349

ABSTRACT:
Peptidomimetics of the formula C.beta.X where C is cysteine, X is any naturally occuring amino acid, and .beta. is a hydrophobic spacer, most notably 2-phenyl-4-aminobenzoic acid. These compounds are effective inhibitors of p2lras farnesyltrasferase, block Ras-dependent oncogenic signalling and inhibit human tumor growth in vivo in animal models. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also disclosed.

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Hancock et al, "A polybsic Domain or Palmitoylation is Required in Addition to the CAAX Motif to Localize p21.sup.ras in the Plasma Membrane", Cell. vol. 63. Oct. 5, 1990, pp. 133-139.
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Willumsen et al. "The p21 ras C-terminus is required for transformation and membrane association," Nature, vol. 310. Aug. 16, 1984, pp. 583-586.

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