Thalidomide metabolite inhibits tumor cell attachment to concanavalin A coated surfaces

The inhibitory effect of drug treatment on tumor cell attachment to plastic surfaces coated with concanavalin A correlates well with the $\text{in}\text{vivo}$ teratogenicity of the drug. Using attachment as an assay, the effects of thalidomide and some of its metabolites have been examined for inhibitory activity. While thalidomide and its hydrolysis products did not alter attachment, metabolites of thalidomide produced by incubation of the drug with murine liver microsomes were inhibitory. Generation of inhibitory products required the presence of glucose-6-phosphate, NADP, glucose-6-phosphate dehydrogenase and magnesium chloride. The degree of inhibition was dependent on the duration of incubation at 37°C. These results suggest a model for the teratogenic action of thalidomide in which metabolites of the drug alter cell surface function leading to interference with normal morphogenic cell to cell interactions.