Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as
desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects
in vivo and
in vitro by a novel drugs
mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation
initiation. As with pateamine A, as described herein, suitable analogs cause
cell cycle arrest or induce
apoptosis in transformed cells. However,
toxicity of such compounds to
slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation
initiation factors and are useful as anticancer and
antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evalutaion of
eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.