Мы используем файлы cookie.
Продолжая использовать сайт, вы даете свое согласие на работу с этими файлами.
Experimental cancer drugs
ZB716
Другие языки:

    ZB716

    Подписчиков: 0, рейтинг: 0
    ZB716
    ZB716.svg
    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
    Drug class Antiestrogen; Selective estrogen receptor degrader
    Identifiers
    • [(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
    PubChem CID
    UNII
    Chemical and physical data
    Formula C32H48BF5O4S
    Molar mass 634.59 g·mol−1
    3D model (JSmol)
    Melting point 230 °C (446 °F) (decomposes)
    • 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=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

    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 (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. 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.

    Clinical Development

    As of December 2020, it is in a phase I clinical trial for ER+/HER2- metastatic breast cancer.

    See also



    Новое сообщение