When SPRMs bind to the<unk>  receptor, the equilibrium between the two conformational states is more closely balanced and hence more easily perturbed by differences in the cellular environment. In tissues where the concentration of coactivators is higher than corepressors, the excess coactivators drive the equilibrium in the agonist direction. Conversely in tissues where corepressor concentration is higher the equilibrium is driven in the antagonist direction. Hence SPRMs display agonist activity in tissues where coactivators predominate and antagonist activity where corepressors are in excess. When inactive the<unk>  receptor, as for other steroid receptor, forms a complex consisting of itself, heat shock proteins (hsp70, hsp90) and immunophilins. Upon activation, due to hormone binding to ligand binding pocket, the receptor complex has been shown to dissociate, triggering nuclear import and giving the receptor the property of dimerisation (Fig. 3). In the nucleus the dimer interacts with<unk>  hormone response element in the DNA causing upregulation or downregulation of the gene. Various studies have demonstrated that it affects expression of up to 100 different genes, depending on receptor isomer. In the action of agonism there occur conformational changes, where alpha helices 3, 4 and 12 create a docking surface for coactivator proteins, which act as bridging factors between the receptor and the general transcription machinery. However, the antagonist prevents proper packing of alpha helix 12 against helices 3 and 4, impairing the receptor’s ability to interact with coactivators, which allows recruitment of corepressor, such as SMRT and NCoR. Due to the minimal recruitment of corepressors during agonist binding then there has been postulated by Liu et al., 2002, that the ratio between coactivators vs. corepressors recruitment might be the determinant whether compound is considered to be an agonist, antagonist or mixed agonist-antagonist. The<unk> s have been described as agents with mixed agonist-antagonist activity and thus the mechanism of action must be due to a balance of these functions.
Selective progesterone receptor modulator
Selective estrogen receptor modulator
Selective androgen receptor modulator
N-Terminal domain antiandrogen
Selective estrogen receptor degrader
Steroidal aromatase inhibitor
Antiprogestogen
Antiestrogen