Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase

JT Hunt, VG Lee, K Leftheris, B Seizinger…

Index: Hunt, John T.; Lee, Ving G.; Leftheris, Katerina; Seizinger, Bernd; Carboni, Joan; et al. J. Med. Chem., 1996 , vol. 39, # 2 p. 353 - 358

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Citation Number: 114

Abstract

All previously reported CAAX-based farnesyltransferase inhibitors contain a thiol functionality. We report that attachment of the 4-imidazolyl group, via 1-, 2-, or 3-carbon alkyl or alkanoyl spacers, to Val-Tic-Met or tLeu-Tic-Gln provides potent FT inhibitors.(R*)-N-[[1, 2, 3, 4-Tetrahydro-2-[N-[2-(1 H-imidazol-4-yl) ethyl]-l-valyl]-3-isoquinolinyl] carbonyl]-l- methionine ([imidazol-4-yl-ethyl]-Val-Tic-Met), with FT IC50= 0.79 nM, displayed potent ...