Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

Identification of Novel Dual-Target Estrogen Receptor α Degraders with Tubulin Inhibitory Activity for the Treatment of Endocrine-Resistant Breast Cancer

“…Further structural modification indicated that incorporating a side chain into OBHSA could improve ERα degradation potency . Based on ER-privileged antagonism skeletons OBHS and OBHSA, we designed and synthesized some dual-functional compounds with good biological activity against BC (Figure ); however, the therapeutic potential of these compounds against endocrine-resistant BC remains to be investigated. − In previous work, a class of dual-target compounds with the potential to treat resistant BC was obtained by introducing phenylselenyl into OBHS, demonstrating the modifiability of OBHS skeleton, but showing no degradation activity against ERα . Given the significant role of microtubules in BC progress and based on the above findings, we proposed to design and synthesize ERα and tubulin dual-target compounds following the structure-based design strategy.…”