Inhibitors of farnesyl-protein transferase

Details Inhibitors of farnesyl-protein transferase Inhibitors of farnesyl-protein transferase

1996-07-17

1997-09-02

Ramsuer, Robert W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514908, 549349, 4352541, A61K 31535, C07D49304

Patent

active

056631936

ABSTRACT:
The present invention is directed to non-peptide compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention also relates to the process for the preparation of a compound of this invention by cultivating a culture of Phoma sp. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

REFERENCES:
patent: 5082489 (1992-01-01), Watson et al.
patent: 5141851 (1992-08-01), Brown et al.
patent: 5151529 (1992-09-01), Sato et al.
patent: 5238922 (1993-08-01), Graham et al.
patent: 5245061 (1993-09-01), Singh
patent: 5254727 (1993-10-01), Dufresne et al.
patent: 5260465 (1993-11-01), Singh et al.
patent: 5260479 (1993-11-01), Singh
patent: 5310949 (1994-05-01), Dufresne et al.
patent: 5326773 (1994-07-01), Desolms et al.
patent: 5340828 (1994-08-01), Graham et al.
patent: 5352705 (1994-10-01), Deana et al.
patent: 5364948 (1994-11-01), Harris et al.
patent: 5420157 (1995-05-01), Singh et al.
patent: 5498627 (1996-03-01), Ishii et al.
patent: 5510371 (1996-04-01), Singh et al.
patent: 5534537 (1996-07-01), Ciccarone et al.
Gibbs, J.B., et al., "Selective Inhibition of Farnesyl-Protein Transferase Blocks Ras Processing In Vivo," The Jour. of Biol. Chem., vol. 268, No. 11, pp. 7617-7620 (1993).
Goldstein, J.L., et al., "Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase," The Jour. of Biol. Chem., No. 24, pp. 15575-15578 (1991).
James, G.L., et al., "Benzodiazepine Peptidomimetics:Potent Inhibitors of Ras Farnesylation in Animal Cells", Science, vol. 260, pp. 1937-1942 (1993).
Kohl, N.E., et al., "Protein Farnesyltransferase Inhibitors Block the Growth of Ras-dependent Tumors in Nude Mice", Proc. Natl. Acad. Sci., USA, vol. 91, pp. 9141-9145 (1994).
Kohl, N.E., et al., "Selective Inhibition of Ras-Dependent Transformation by a Farnesyltransferase Inhibitor", Science, vol. 260, pp. 1934-1937 (1993).
Pompliano, D.L., et al., "Steady-State Kinetic Mechanism of Ras Farnesyl:Protein Transferase", Biochemistry, vol. 31, pp. 3800-3807 (1992).
Qian, T., et al. "Design and Structural Requirements of Potent Peptidomimetic Inhibitors of p21 Ras Farnesyltransferase", The Jour. of Biol. Chem., vol. 269, No. 17, Issue of Apr. 29, pp. 12410-12413 (1994).
Reiss, Y., "Inhibition of Purified p21ras Farnesyl: Protein Transferase by Cys-AAX Tetrapeptides", Cell, vol. 62, pp. 81-88 (1990).
Reiss, Y., et al., "Sequences Requirement for Peptide Recognition by Rat Brain p21 Ras Protein Farnesyltransferase," Proc. Natl. Acad. Sci., USA, 88 pp. 732-736 (1991).
Schaber, M.D., et al., "Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase", The Jour. of Biol. Chem., vol. 365, No. 25, pp. 14701-14704 (1990).
Schulz, S. and Nyce, J.W., "Inhibition of Protein Farnesyltransferase: A Possible Mechanism of Tumor Prevention by Dehydroepiandrosterone Sulfate," Carcinogenesis, vol. 15, No. 11, pp. 2649-2652 (1994).
Lorenzino, L.S., et al., "A Peptidomimetic Inhibitor of Farnesyl:Protein Transferase Blocks the Anchorage-dependent and independent Growth of Human Tumor Cell Lines," Cancer Research, vol. 55, pp. 5302-5309, Nov. 15, 1995.
Kohl, N.E., et al., "Inhibition of Farnesyltransferase Induces Regression of Mammary and Salivary Carcinomas in Ras Transgenic Mice," Nature Medicine, vol. 1, No. 8 (Aug. 1995).

Affiliated with

Also associated with

Rating

Inhibitors of farnesyl-protein transferase does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibitors of farnesyl-protein transferase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitors of farnesyl-protein transferase will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-308605