MOLECULAR PHARMACOLOGY OF METHYL-3,5-DIIODO-4 (4'METHOXYPHENOXY) BENZOATE (DIME) AND ITS NON-HYDROLYZIBLE ETHANONE ANALOG (DIPE) (REVIEW)

A molecular structural relationship of thyroid hormones to methyl-3,5- diiodo-4-(4'-methoxy-phenoxy) benzoate (DIME) and [3,5-diiodo-4-(4'-me thoxyphenoxy)phenyl]-ehtanone) (DIPE) and to apoptosis-mediated metamo rphogenic mechanisms is postulated. DIME disrupts microtubule assembly already in anaphase, preparing cells for G2/M block, chromosome aggre gation and caspase-3 mediated apoptosis. Cooperative action of DIME an d vincristine, defining mutually exclusive cellular sites, identifies microtubules as primary drug targets followed by downstream cellular c onsequences, leading to cell death. Absence of in vivo toxicity of DIM E appears to be related to impermeability to DIME of normal cells, but not of turner cells in vivo. Normal tissue cells hydrolyze DIME but m ost tumor cells, except lung cancer cells, do not. DIPE, being resista nt to enzymatic hydrolysis, is equally effective in all tumor cells.