Inhibitors of prenyl transferases

Details Inhibitors of prenyl transferases Inhibitors of prenyl transferases

1996-01-11

1999-10-12

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530331, 564336, 564337, 562557, 562559, A61K 3805

Patent

active

059655399

ABSTRACT:
Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.

REFERENCES:
patent: 5043268 (1991-08-01), Stock
patent: 5141851 (1992-08-01), Brown et al.
patent: 5238922 (1993-08-01), Graham et al.
Gibbs, J.B., Ras C-Terminal Processing Enzymes-New Drug Targets, Cell, 65:1-4 (1991).
Gibbs et al., Farnesyltransferase Inhibitors: Ras Research Yields a Potential Cancer Terapeutic, Cell, 77:175-178 (1994).
Brown et al., Tetrapeptide inhibitors of protein farnesyltransferase: Amino-terminal substitution in phenylalanine-containing tetrapeptides restores farnesylation, Proc. Natl. Acad. Sci. U.S.A., 89:8313-8316, (1992).
Hancock et al, "A polybasic Domain or Palmitoylation is Required in Addition to the CAAX Motif to Localize p21.sup.ras to the Plasma Membrane", Cell, vol. 63, Oct. 5, 1990, pp. 133-139.
Reiss et al, "Inhibition of Purified p21.sup.ras Farnesyl: Protein Transferase by Cys-AAX Tetrapeptides", Cell, vol. 62, Jul. 13, 1990, pp. 81-88.
Willumsen et al, "The p21 ras C-terminus is required for transformation and membrane association," Nature, vol. 310, Aug. 16, 1984, pp. 583-586.
Kohl et al., Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor, Science, 260:1934-1937 (1993).
Graham et al., Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase, J. Med. Chem., 37:725-732 (1994).
Garcia et al., Peptidomimetic Inhibitors of Ras Farnesylation and Function in Whole Cells, J. Biol. Chem., 268:18415-18418 (1993).
Nigam et al., Potent Inhibition of Human Tumor p21.sup.ras Farnesyltransferase by A.sub.1 A.sub.2 -lacking p21.sup.ras CA.sub.1 A.sub.2 X Peptidomimetics, J. Biol. Chem., 268:20695-20698 (1993).
Qian et al., Design and Structural Requirements of Potent Peptidomimetic Inhibitors of p21.sup.ras Farnesyltransferase, J. Biol. Chem., 269:12410-12413 (1994).
Qian et al., Peptidomimetic Inhibitors of P21RAS Farnesyltransferase: Hydrophobic Functionalization Leads to Disruption of P21RAS Membrane Association in Whole Cells, Bioorg. Med. Chem. Lett., 4:2579-2584 (1994).
Goldstein et al., Benzodiazepine Peptidometics: Potent Inhibitors of Ras Farnesylation in Animal Cells, Science, 260:1937-1942 (1993).
Reiss et al., Inhibition of Purified p21.sup.ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides, Cell, 62:81-88 (1990).
Vogt et al., A Non-peptide Mimetic of Ras-CAAX:Selective Inhibition of Farnesyltransferase and Ras Processing, (1995) J. Biol. Chem. 270:660-664.
Kohl et al., Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice, (1994) Proc. Natl. Acad. Sci. USA 91:9141-9145.
Cox et al., The CAAX Peptidomimetic Compound B581 Specifically Blocks Farnesylated, but Not Geranylgeranylated or Myristylated, Oncogenic Ras Signaling and Transformation, (1994) J. Biol. Chem. 269:19203-19206.
Lerner et al., Ras CAAX Peptidomimetic FTI-277 Selectively Blocks Oncogenic Ras Signaling by Inducing Cytoplasmic Accumulation of Inactive Ras-Raf Complexes (1995) J. Biol. Chem. 270:26802-26806.
Sun et al., Ras CAAX Peptidomimetic FTI 276 Selectively Blocks Tumor Growth in Nude Mice of a Human Lung Carcinoma with K-Ras Mutation and p53 Deletion, (1995) Cancer Research 55, 4243-4247.

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