Open AccessGLL398, an oral selective estrogen receptor degrader (SERD), blocks tumor growth in xenograft breast cancer models
Author(s) -
Shuai Guo,
Changde Zhang,
Madhusoodanan Mottamal,
Ahamed Hossain,
Jiawang Liu,
Guangdi Wang
Publication year - 2020
Publication title -
breast cancer research and treatment
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.908
H-Index - 154
eISSN - 1573-7217
pISSN - 0167-6806
DOI - 10.1007/s10549-020-05558-w
Subject(s) - fulvestrant , breast cancer , cancer research , pharmacology , estrogen receptor , cancer , medicine , pharmacokinetics , chemistry
Selective estrogen receptor degrader (SERD) has proven clinically effective in treating advanced or metastatic breast cancer since the approval of fulvestrant by FDA in 2002. Recent expansion of indications as a first line monotherapy and as combination therapy with CDK4/6 inhibitors further extends its clinical utility as an efficacious breast cancer endocrine regimen. However, the poor pharmacokinetic properties of fulvestrant and its injection-only administration route has driven continued efforts to develop orally bioavailability SERD that could potentially improve clinical response to SERD treatment. GLL398, a boron-modified GW5638 analog, showed superior oral bioavailability, while retaining both antiestrogenic activity and ER degrading efficacy at a potency level comparable to the more active metabolite of GW5638, GW7604.