ZB716

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.^[1] The drug is a silent antagonist of the ERα (IC₅₀ = 4.1 nM) as well as a selective estrogen receptor degrader (SERD).^[1] It is an analogue and prodrug of fulvestrant in which the C3 hydroxyl group has been replaced with a boronic acid moiety.^[1] In accordance, the two drugs have similar pharmacodynamic properties.^[1] 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.^[1]

Other namesFulvestrant-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

Routes of
administrationBy mouth^[1]

Drug classAntiestrogen; Selective estrogen receptor degrader

CAS Number

• 1853279-29-4 ^Y

Quick facts Clinical data, Other names ...

ZB716

Clinical data
Other names	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
Routes of administration	By mouth[1]
Drug class	Antiestrogen; Selective estrogen receptor degrader
Identifiers
IUPAC name [(7R,8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl]boronic acid
CAS Number	1853279-29-4 Y
PubChem CID	126480615
UNII	E35ZN95LMT
Chemical and physical data
Formula	C32H48BF5O4S
Molar mass	634.59 g·mol−1
3D model (JSmol)	Interactive image
Melting point	230 °C (446 °F) (decomposes)
SMILES B(C1=CC2=C(C=C1)[C@H]3CC[C@]4([C@H]([C@@H]3[C@@H](C2)CCCCCCCCCS(=O)CCCC(C(F)(F)F)(F)F)CC[C@@H]4O)C)(O)O
InChI InChI=1S/C32H48BF5O4S/c1-30-17-15-26-25-12-11-24(33(40)41)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-43(42)19-9-16-31(34,35)32(36,37)38/h11-12,21-22,26-29,39-41H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,43?/m1/s1 Key:FIAYIYKWRBIBQG-GDWZZRAASA-N

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A single oral dose of 8.3 mg/kg ZB716 to mice has been found to result in an over 160 ng/mL (160,000 pg/mL) maximal concentration of the drug in circulation, a level far in excess of the 15.2 ng/mL (15,200 pg/mL) concentration achieved with subcutaneous injection of fulvestrant in mice.^[1] 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.^[1]

ZB716 produces fulvestrant as an active metabolite in vivo in mice, with approximately 10 to 15% of the drug being converted into it.^[1] As such, most of the effects are likely due to the parent drug.^[1]