title: 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 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.
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Jiawang
authors.initials: J
authors.lastname: Liu
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Shilong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, Louisiana 70112, United States.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Akerstrom
authors.affiliation: Xiamen Medichance Laboratory , Xiamen 361022, China.
authors.forename: Chester
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Xiamen Medichance Laboratory , Xiamen 361022, China.
authors.forename: Youning
authors.initials: Y
authors.lastname: Ma
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Changde
authors.initials: C
authors.lastname: Zhang
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Shanchun
authors.initials: S
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Skripnikova
authors.affiliation: College of Pharmacy, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Melyssa R
authors.initials: MR
authors.lastname: Bratton
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, Louisiana 70112, United States.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pannuti
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, Louisiana 70112, United States.
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.affiliation: College of Pharmacy, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wiese
authors.affiliation: RCMI Cancer Research Center, Xavier University of Louisiana , New Orleans, Louisiana 70125, United States.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction; D013237:Stereoisomerism; D013261:Sterols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D005466:Fluorocarbons
chemical_list: D001897:Boronic Acids; D047628:Estrogen Receptor alpha; D020845:Selective Estrogen Receptor Modulators; D013261:Sterols; D013629:Tamoxifen; C000621128:ZB716 compound; D005466:Fluorocarbons