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Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).

ABSTRACT: Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ER? competitively (IC50 = 4.1 nM) and effectively downregulates ER? in both tamoxifen-sensitive and tamoxifen-resistant breast cancer cells. Furthermore, It has superior oral bioavailability (AUC = 2547.1 ng·h/mL) in mice, indicating its promising clinical utility as an oral SERD.

SUBMITTER: Liu J 

PROVIDER: S-EPMC5499704 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).

Liu Jiawang J   Zheng Shilong S   Akerstrom Victoria L VL   Yuan Chester C   Ma Youning Y   Zhong Qiu Q   Zhang Changde C   Zhang Qiang Q   Guo Shanchun S   Ma Peng P   Skripnikova Elena V EV   Bratton Melyssa R MR   Pannuti Antonio A   Miele Lucio L   Wiese Thomas E TE   Wang Guangdi G  

Journal of medicinal chemistry 20160829 17

Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC50 = 4.1 nM) and effectively downregulates ERα in both tamoxifen-sensitive and tamoxifen-resistant breast cancer cells. Furthermore, It has superior oral bioavailability (AUC = 2547.  ...[more]

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