LSZ102

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

LSZ102 是一种有效的、口服生物可利用的选择性雌激素受体降解剂 (SERD)，ERα 转录 IC50 为 6 nM，ERα 降解 IC50 为 0.2 nM。

LSZ102 is a potent, orally bioavailable, selective estrogen receptor degrader (SERD) with ERα transcription IC50 of 6 nM and ERα degradation IC50 of 0.2 nM; robustly causes inhibition of cell proliferation in MCF-7 cells with IC50 of 1.7 nM, inhibits the mRNA level of canonical endogenous ER target gene GREB1 with IC50 of 8.9 nM; demonstrates anti-tumor efficacy in the ER+ human breast cancer MCF-7 xenograft model (10 mg/kg).Breast Cancer Phase 1 Clinical.

LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC50 of 0.2 nM and currently in Phase I/Ib trials for the treatment of ERα positive breast cancer. LSZ-102 induces significant degradation of ERα after 24 h, when given as a 10 μM solution to MCF-7 cells. Robust inhibition of cell proliferation in MCF-7 cells is observed upon incubation with LSZ-102 with a half inhibitory concentration of 1.7 nM. Results demonstrate that LSZ-102 effectively inhibits the estrogen-induced activation of the ERE-luciferase reporter using charcoal-stripped serum treated with E2 with IC50 of 0.3 nM.

Treatment of the mice with LSZ-102 once daily at 20 mg/kg results in significant tumor growth inhibition as compare to the control group treated with vehicle alone, resulting in tumor stasis (mean change in tumor volume of LSZ-102 vs control=%ΔT/ΔC of 2.4% on day 48, p<0.05). Dosing of 3 mg/kg solution of LSZ-102 in male Sprague-Dawley rats results in 33% bioavailability and a dose-normalized exposure of 620 nM?h.

LSZ 102 | LSZ-102

Endocrinology/Hormones

Estrogen Receptor/ERR

Estrogen Receptor/ERR

Cancer

Breast Cancer

2135600-76-7

470.462

C25H17F3O4S

>98% (HPLC)

DMSO : 100 mg/mL 212.56 mM; H2O : < 0.1 mg/mL

O=C(O)/C=C/C1=CC=C(OC2=C(C3=CC=C(F)C=C3C(F)(F)C)SC4=CC(O)=CC=C42)C=C1

(E)-3-(4-((2-(2-(1,1-Difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

(-20℃)

With Ice Pack

≥ 2 years