11. Exploring the Role of the Linker in the Antiestrogen Activities of Tamoxifen Conjugates

Xinyi Li Rose-Hulman Institute of Technology
Faculty Sponsor(s): Ross Weatherman Rose-Hulman Institute of Technology
Tamoxifen is a selective estrogen receptor modulator (SERM) used for both early and advanced hormone-receptor-positive breast cancer treatment. Tamoxifen can stop the growth of breast cancer cells by blocking the connection between estrogen and estrogen receptors (ER). However, long term usage of tamoxifen may cause serious side effects such as hot flashes and uterine cancer. And eventually, breast cancer cells can grow resistance to tamoxifen. So scientists are working to develop novel breast cancer drugs, tamoxifen derivatives, which can overcome the problems with resistance. Previous work in the Weatherman lab has shown that attaching large bulky groups off of the basic side chain of tamoxifen can increase the potency of those analogs against tamoxifen-resistant breast cancer cells. Therefore, we have synthesized a novel tamoxifen derivative with a 1,3-phenylenedimethanamine linker using a 3-step synthesis method. The ER binding ability of the tamoxifen derivative in vitro was studied by utilizing a fluorescence polarization assay (λex=490nm and λem=510nm). The positive control of this polarization assay was raloxifene which is an excellent drug for breast cancer treatment. Additionally, a dual luciferase reporter assay will be utilized in breast cancer cell lines to test the effect of the tamoxifen conjugate on ER-mediated transcription. In conclusion, the results acquired so far suggested that this novel tamoxifen derivative could be a potential drug for breast cancer treatment.
Chemistry
Poster Presentation

When & Where

Irwin Library 1st Floor