|Synonyms||Fulvestrant-3-boronic acid; Fulvestrant-3-boronoate; 7α-[9-[(4,4,5,5,5-Pentafluoropentyl)-sulfinyl]nonyl]-3-(dihydroxy-boryl)estra-1,3,5(10)-trien-17β-ol|
|Drug class||Antiestrogen; Selective estrogen receptor degrader|
|Chemical and physical data|
|Molar mass||634.594 g/mol g·mol−1|
|3D model (JSmol)|
|Melting point||230 °C (446 °F) (decomposes)|
ZB716, also known as fulvestrant-3-boronic acid, is a synthetic, steroidal, orally active antiestrogen which is under development for the treatment of estrogen receptor (ER)-positive metastatic breast cancer. The drug is a silent antagonist of the ERα (IC50 = 4.1 nM) as well as a selective estrogen receptor degrader (SERD). It is an analogue of fulvestrant in which the C3 hydroxyl group has been replaced with a boronic acid moiety. In accordance, the two drugs have similar pharmacodynamic properties. However, whereas fulvestrant is not orally active and must be administered via intramuscular injection, ZB716 is less susceptible to first-pass metabolism, and in relation to this, is orally active.
A single oral dose of 8.3 mg/kg ZB716 to mice has been found to result in an over 160 ng/mL maximal concentration of the drug in circulation, a level far in excess of the 15.2 ng/mL concentration achieved with subcutaneous injection of fulvestrant in mice. As such, not only may ZB716 be more convenient to administer in humans, it has far greater bioavailability compared to fulvestrant and hence may allow for greater systemic exposure and therapeutic benefit.
ZB716 produces fulvestrant as an active metabolite in vivo in mice, with approximately 10 to 15% of the drug being converted into it. As such, most of the effects are likely due to the parent drug.
- Liu J, Zheng S, Akerstrom VL, Yuan C, Ma Y, Zhong Q, Zhang C, Zhang Q, Guo S, Ma P, Skripnikova EV, Bratton MR, Pannuti A, Miele L, Wiese TE, Wang G (2016). "Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD)". J. Med. Chem. 59 (17): 8134–40. doi:10.1021/acs.jmedchem.6b00753. PMC 5499704. PMID 27529700.
- Zhang C, Guo S, Yang L, Liu J, Zheng S, Zhong Q, Zhang Q, Wang G (November 2017). "Metabolism, pharmacokinetics, and bioavailability of ZB716, a Steroidal Selective Estrogen Receptor Downregulator (SERD)". Oncotarget. 8 (61): 103874–103889. doi:10.18632/oncotarget.21808. PMC 5732773. PMID 29262607.
- Guo S, Zhang C, Bratton M, Mottamal M, Liu J, Ma P, Zheng S, Zhong Q, Yang L, Wiese TE, Wu Y, Ellis MJ, Matossian M, Burow ME, Miele L, Houtman R, Wang G (January 2018). "ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models". Oncotarget. 9 (6): 6924–6937. doi:10.18632/oncotarget.24023. PMC 5805526. PMID 29467940.
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