Inhibitors of farnesyl-protein transferase

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

1994-06-06

1996-04-23

Ivy, C. Warren

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514547, 549267, 560180, 560181, 560 55, 560 60, A61K 31335, A61K 31225

Patent

active

055103715

ABSTRACT:
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. 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: 5043268 (1991-08-01), Stock
patent: 5141851 (1992-08-01), Brown et al.
patent: 5245061 (1993-09-01), Singh
patent: 5260465 (1993-11-01), Singh et al.
patent: 5260479 (1993-11-01), Singh
patent: 5276217 (1994-01-01), Tius
Bos, J. L. "ras Oncogenes in Human Cancer: A Review", Cancer Research, vol. 49, pp. 4682-4689 (1989).
Gibbs, J. B., "Ras C-Terminal Processing Enzymes New Drug Targets?", Cell, vol. 65, 1-4 (1991).
Gibbs, J. B. et al., "Selective Inhibition of Farnesyl-Protein Transferase Blocks Ras Processing in Vivo", The Journal of Biological Chemistry, vol. 268, No. 11, pp. 7617-7620 (1993).
Goldstein, J. L. et al., "Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase", The Journal of Biological Chemistry, vol. 266, No. 24, pp. 15575-15578 (1991).
James, G. L. et al., "Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farnesylation in Animal Cells", Sciences, vol. 260, pp. 1937-1942 (1993).
Kohl, N. E. et al., "Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor", Science, vol. 260, pp. 1934-1937 (1993).
Leftheris, K. et al., Peptide Based P21RAS Farnesyl Transferase Inhibitors: Systematic Modification of the Tetrapeptide CA1A2X Motif, (1994), Bioorganic & Medicinal Chemistry Letters, 4, No. 7, pp. 887-892.
Pompliano, D. L. et al., Steady-State Kinetic Mechanism of Ras Farnesyl: Protein Transferase, (1992), Biochemistry, 31 pp. 3800-3807.
Qian, Y et al., Design and Structural Requirements of Potent Peptidomimetic Inhibitors of p21ras Farnesyltransferase, (1994), The Journal of Biological Chemistry, 269, No. 17, pp. 12410-12413.
Reiss, Y. et al., Inhibition of Purified p21ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides, (1990), Cell 62, pp. 81-88.
Reiss, Y et al., Sequence requirement for peptide recognition by rat brain p21 ras protein farnesyltransferase, (1991), Proc. Natl. Acad. Sci. USA, 88, pp. 732-736.
Schaber, M. D. et al., Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase, (1990), The Journal of Biological Chemistry, 265, No. 25, pp. 14701-14704.
Singh, S. B. et al., "Fusidienol: A Novel Inhibitor of Ras Farnesyl-Protein Transferase from Fusidium griseum", Tetrahedron Letters, vol. 35, No. 27, pp. 4693-4696 (1994).
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).
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).

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-2308781