LSZ-102

Cas No.:	2135600-76-7
Chemical Name:	LSZ-102
Synonyms:	LSZ-102;LSZ102;(E)-3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid;Q50825475;(E) -3- (4-((2-(2- (1,1-Difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic Acid;0Y175XGX4P;BDBM269484;BCP29222;NSC814025;DB15362;US10058534, 139;FC(C)(F)C1=C(C=CC(=C1)F)C1=C(C2=C(S1)C=C(C=C2)O)OC1=CC=C(C=C1)/C=C/C(=O)O;(2E)-3-[4-({2-[2-(1
SMILES:	S1C2C=C(C=CC=2C(=C1C1C=CC(=CC=1C(C)(F)F)F)OC1C=CC(/C=C/C(=O)O)=CC=1)O
Formula:	C25H17F3O4S
M.Wt:	470.462
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC50 of 0.2 nM.
Target:	estrogen receptor[1]
In Vivo:	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[1].
In Vitro:	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[1].
Kinase Assay:	Growth factors depleted MCF-7 ERE-luc cells are used and seeded (10 000 cells/well) in 96-well plates in CSS medium. After overnight incubation, cells are treated with LSZ-102 in the presence of estradiol (0.1 nM) for 24 h. Cells are then lysed and quantified for luciferase activity using Bright-Glo assay[1].
Animal Administration:	Female athymic nude mice are used for tumor xenograft studies. MCF-7 cells are subcutaneously injected (200 μL/animal) in the right axillary mammary fat pad area. Tumor volume and body weights are measured twice weekly. When tumors reach an average volume of ~200 mm3, mice are randomized into different groups. Animals are orally administered vehicle alone or 20 mg/kg LSZ-102 daily or 60 mg/kg tamoxifen 5 days per week[1].
References:	[1]. Tria GS, et al. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.