LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC₅₀ of 0.2 nM.

estrogen receptor^[1]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

470.46

C₂₅H₁₇F₃O₄S

2135600-76-7

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

DMSO : 100 mg/mL (212.56 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (insoluble)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1.67 mg/mL (3.55 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.55 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 1.67 mg/mL (3.55 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.55 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 1.67 mg/mL (3.55 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.55 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.