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

  • J Med Chem. 2016 Sep 8;59(17):8134-40. doi: 10.1021/acs.jmedchem.6b00753.
Jiawang Liu  1 ,  Shilong Zheng  1 ,  Victoria L Akerstrom  2 ,  Chester Yuan  3 ,  Youning Ma  3 ,  Qiu Zhong  1 ,  Changde Zhang  1 ,  Qiang Zhang  1 ,  Shanchun Guo  1 ,  Peng Ma  4 ,  Elena V Skripnikova  4 ,  Melyssa R Bratton  4 ,  Antonio Pannuti  2 ,  Lucio Miele  2 ,  Thomas E Wiese  4 ,  Guangdi Wang  1
Affiliations
  • 1. RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
  • 2. Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, Louisiana 70112, United States.
  • 3. Xiamen Medichance Laboratory , Xiamen 361022, China.
  • 4. College of Pharmacy, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
PMID: 27529700 DOI: 10.1021/acs.jmedchem.6b00753
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 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 = 2547.1 ng·h/mL) in mice, indicating its promising clinical utility as an oral SERD.

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