Richard R Gibbs

US Patent:

6586461, Jul 1, 2003

Filed:

Jun 16, 1999

Appl. No.:

09/334704

Inventors:

Richard A. Gibbs - Detroit MI

Assignee:

Wayne State University - Detroit MI

International Classification:

A61K 31341

US Classification:

514438, 514461, 549 79, 549497, 558152, 568715

Abstract:

Farnesyl diphosphate analogs, specifically the 3-substituted alcohol precursors of the diphosphate analogs, 3-allylfarnesol and 3-vinylfarnesol, are potent inhibitors of mammalian protein fanesyltransferase (FTase). 3-allylgeranylgeraniol is a highly specific cellular inhibitor of protein geranylgeranylation (GGTase I). Furthermore, these compounds are able to efficiently block the anchorage-dependent growth of ras transformed cells. While 3-allylfarnesol inhibits protein farnesylation in situ, 3-vinylfarnesol instead leads to the abnormal prenylation of proteins with the 3-vinylfarnesyl group. In a similar manner, treatment with 3-allylgeranylgeraniol inhibits protein geranylgeranylation while 3-vinylgeranylgeraniol restores protein geranylgeranylation in cells.

US Patent:

20040121985, Jun 24, 2004

Filed:

Jun 10, 2003

Appl. No.:

10/459122

Inventors:

Richard Gibbs - Detroit MI, US

International Classification:

A61K031/695
A61K031/66
A61K031/381

US Classification:

514/063000, 514/142000, 514/739000, 514/726000, 514/438000, 514/461000, 549/029000, 549/497000, 558/207000, 568/809000

Abstract:

Farnesyl diphosphate analogs, specifically the 3-substituted alcohol precursors of the diphosphate analogs, 3-allylfarnesol and 3-vinylfarnesol, are potent inhibitors of mammalian protein fanesyltransferase (FTase). 3-allylgeranylgeraniol is a highly specific cellular inhibitor of protein geranylgeranylation (GGTase I). Furthermore, these compounds are able to efficiently block the anchorage-dependent growth of ras transformed cells. While 3-allylfarnesol inhibits protein farnesylation in situ, 3-vinylfarnesol instead leads to the abnormal prenylation of proteins with the 3-vinylfarnesyl group. In a similar manner, treatment with 3-allylgeranylgeraniol inhibits protein geranylgeranylation while 3-vinylgeranylgeraniol restores protein geranylgeranylation in cells.