Tamoxifen Analogs Sample Clauses

Tamoxifen Analogs. Tamoxifen is an antagonist of the estrogen receptor (ER) in breast tissue. It has been the standard endocrine (anti-estrogen) therapy for hormone-positive early breast cancer in post-menopausal women, although aromatase inhibitors have been proposed. Estrogen binds to and activates the estrogen receptor of some breast cancer cells which require estrogen for growth. Tamoxifen is metabolized into compounds that also bind to the estrogen receptor but do not activate it. Because of this competitive antagonism, tamoxifen acts as a key broken off in the lock that prevents any other key from being inserted, preventing estrogen from binding to ER ligand binding domain [12]. Tamoxifen was prepared and docked into ER-α and LRH-1 with the same procedures as for the SID-7969543 analogs (Figure 3.7). In ER-α, the core structure of tamoxifen is composed of one double bond and three attached phenyl rings located in the center of the hydrophobic pocket. The dimethylamine head points to the H12 region and prevents H12 from folding into its active form. In LRH-1, the core structure of tamoxifen also sits in the center of the hydrophobic pocket, but the protonated dimethylamine head points into tunnel C. The cis- phenyl ring is in the non-polar pocket N1. With this pose, tamoxifen does not show any potential conflicts with H12.
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