Bisphenol AR Modulators Targeting NTD for Prostate Cancer

The patent develops AR inhibitors with dual functionality: they can bind to and inhibit both full-length AR and truncated AR splice variants. The compounds are designed to interact with the N-terminal domain (NTD) of AR, which is present in both full-length and truncated variants, thereby achieving universal inhibition across different AR forms and overcoming the limitation of existing inhibitors that only target full-length AR.

The patent employs parameter changes by modifying the chemical structure of AR inhibitors to enhance their binding affinity and specificity for the N-terminal domain of AR. By adjusting molecular parameters such as substituent groups on the core structure, the inhibitors are optimized to effectively target both full-length and truncated AR splice variants, thereby improving treatment reliability.

The patent applies preliminary action by designing inhibitors that proactively target the N-terminal domain of AR, which is constitutively active and drives castration-resistant disease. By preemptively blocking this domain, the inhibitors prevent the development of castration-resistant prostate cancer rather than merely responding to it, thereby extending the duration of treatment effectiveness.

The patent uses the N-terminal domain of AR as an intermediary target. Instead of directly targeting the ligand-binding domain, the inhibitors bind to the NTD, which acts as a mediator to suppress AR activity upstream. This intermediary approach allows the inhibitors to effectively block both androgen-dependent and androgen-independent AR signaling pathways, prolonging treatment duration.