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Pippione et al. Steroidogenic enzymes in prostate cancer
Figure 15: Selected competitive hormone antagonists under development
Figure 16: Selected examples of BF-3 site modulators
The AR NTD contains amino acids 1-558 and is an translocation. Importantly, also constitutively-
intrinsically disordered region. Activation function-1 active AR splice variants lacking LBD are inhibited
(AF-1) is a protein binding domain known to by EPI analogues where traditional AR antagonists
bind different co-regulators and its low sequence are ineffective [138] . EPI-001 (68), discovered by
identity with other nuclear receptors renders it Andersen et al. [139] by functional assay screening of
an appealing target for selective small molecule marine sponge extracts, is shown in Figure 17; its
inhibitors [117] . The most studied AR NTD modulators stereoisomers EPI-002-EPI-005 have also been
are EPI compounds that have been shown to be isolated and evaluated later. The potential therapeutic
bound covalently to AF-1 and to inhibit AR nuclear benefits of EPI have been demonstrated using
350 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ December 12, 2017
