Competition of tamoxifen with thyroxine for TBG binding: ligand binding assay and computational data

Objective: Tamoxifen, a nonesteroidal antiesterogen, is widely used in the treatment of breast cancer. Recently, the effect of tamoxifen on thyroid function has caused considerable concern, yet the results of different studies are controversial and the precise mechanism of such influence is obscure. In view of the fact that some drugs such as furosemide, diclofenac and mefenamic acid, based on the structural similarities to thyroxine could compete for binding to thyroxine binding globulin (TBG) and appears that there are some structural similarities between tamoxifen and thyroxine, one can hypothesize that tamoxifen is also able to compete for TBG binding and thereby affecting thyroid function tests. Design and methods: In this study, we designed an in vitro binding assay as well as computational methods using MOPAC 7 package for evaluation of competitive potency of tamoxifen for TBG binding in comparison with well-known TBG competitors (including furosemide, mefenamic acid and diclofenac). Results: The result of competition assay and Scatchard analysis revealed that tamoxifen does not bind to TBG at the T4 binding site, thus it is not a thyroxine competitor. Computational results also indicated that structural characteristics of tamoxifen are significantly different from those of T4 and its well-known competitors. Conclusion: In conclusion, the probability of competition between tamoxifen and T4 is ruled out by these results.