ANTICANCER AGENTS BASED ON REGULATION OF PROTEIN PRENYLATION
摘要
Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.
申请公布号
WO0234247(A3)
申请公布日期
2003.01.16
申请号
WO2001US32618
申请日期
2001.10.23
申请人
THE ARIZONA DISEASE CONTROL RESEARCH COMMISSION
发明人
ROSE, SETH, D.;LEFLER, SCOTT, R.;OTTERSBERG, STEVEN, R.;KIM, ANN, Y.;OKOLOTOWICZ, KARL, J.;HARTMAN, ROSEMARIE, F.