text: Functionally, AR NTD plays the primary role in regulating target gene transcription activation and mediating various receptor-protein and intra-receptor N-terminal and C-terminal interactions. Therefore, modulation of NTD function is considered an efficient strategy to target AR action. Among various functional domains in different nuclear receptors, NTD is the least conserved and so could maybe become the best target site for NTD antagonists to achieve AR specificity. However the structural features of the NTD are undetermined due to a high degree of flexibility in its conformation. Both biochemical and circular dichroism spectroscopy analysis suggest that AR NTD is highly disordered under native conditions, making it a difficult target for drug discovery.
  In 2008 there were reports of a chlorinated peptide, sintokamide A, isolated from marine sponges that effectively inhibits AR N-terminal domain-activated reporter gene transcription, see figure 8. The evidence presented was not sufficient to support the conclusion that sintokamide A directly inhibits the function of AR NTD, and the mechanism of action needs further investigation.