Teratogen Metabolism: Spontaneous Decay Hydrolysis Products of Thalidomide and Thalidomide Analogue Are Not Activated by Liver Microsomes

摘要

Thalidomide and two analogues, EM87 and EM12, inhibit the attachment of tumor cells to concanavalin A coated surfaces only if the drugs are treated with hepatic microsomes and cofactors. Pre-incubation of these drugs in buffered saline at 37 C results in a progressive decline in their ability to be activated to inhibitory products. Similarly, post-incubation of the inhibitory products leads to a decline in their ability to inhibit attachment. Decay rates differ for the three compounds. Thalidomide, EM87 and EM12 require 3 hours, 1 hour and 6 hours, respectively, to decline to control levels. These relative rates of decay are consistent with the relative teratogenicity of the three drugs. (ERA citation 09:017444)