Dhandapani Ganapathy and Govindasamy Sekar. To test the feasibility of these conjugates, a 4-hydroxytamoxifen analog was conjugated to a diaminoalkyl linker and then conjugated to activated esters of a poly methacrylic acid polymer synthesized by atom transfer radical polymerization.
This effect would be less of a concern in adults who have stopped growing. The estradiol-protein conjugates have been reported to localize to the plasma membrane and the estradiol-dendrimer conjugate localized to the cytoplasm in ER-positive cells 722 - TriantafillouSteven G. None of the conjugates were capable of activating estrogen-receptor mediated transcription, although their ER antagonist effects were not tested.
The polymer conjugate was then tested for its ability to bind to ER alpha and ER beta using a radiolabeled estradiol competition assay with purified recombinant receptor. Tamoxifen Figure 1compound 1one of the most effective anticancer drugs ever, acts as an antiestrogen in breast tissue, blocking the activity of endogenous estrogens, most notably estradiol 2at the estrogen receptor ER 1.
From Wikipedia, the free encyclopedia. One alternative explanation for the transcriptional activity of the polymer conjugate is that free hydroxytamoxifen analog is present in the sample or is being released by conjugate degradation.
While searching the Internet for some interesting Tamoxifen sources I came across the above cartoon. To the best of our knowledge, this is the first time that a macromolecular conjugate of a hormone has been reported to modulate a nuclear receptor's transcriptional activity.
Retrieved April 7, In this respect Tamoxifen is no different and it is the trans isomer that is the active in the treatment of breast cancer. Retrieved July 3, Macromolecular conjugates of tamoxifen could perhaps be used to circumvent some of the limitations of the extensively used breast cancer drug. Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action.
Please refer to this blog post for more information.
Not only could a covalent tamoxifen macromolecular conjugate potentially have different tissue targeting abilities, but it could also be used to potentially target different subcellular locations inside a cell. The Harvard researchers developed a specific protocol for a golden retriever named Navy who was cancer-free after receiving the prescribed cocktail of celecoxibdoxycyclineand tamoxifen — the treatment subsequently became known as the Navy Protocol.
Journal of Medicinal Chemistry 37 11 ,