SAR439859 (compound 43d) is an orally active, nonsteroidal and selective estrogen receptor degrader (SERD). SAR439859 is a potent ER antagonist and has ER degrading activity with an EC₅₀ of 0.2 nM for ERα degradation^[1]. SAR439859 demonstrates robust antitumor efficacy and limited cross-resistance in ER⁺ breast cancer^[2].

SAR439859 (compound 43d) induces strong in vivo antitumor activity against a variety of BC cell lines and patient-derived xenografts, including models that harbor ERα mutations^[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.

SAR439859 (compound 43d; orally; 2.5-25 mg/kg; twice daily for 30 days) exhibits substantial tumor-growth inhibition and displays tumor regression at the dose of 25 mg/kg/BID^[1].
SAR439859 (3 mg/kg for iv and 10 mg/kg for po) shows a low to moderate clearance in the three animal species tested (0.03-1.92 L/h•kg), low to moderate volume of distribution (V_ss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T_1/2 was variable across species (1.98 h in mouse, 4.13 h in rat and 9.80 h in dog)^[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.

554.48

C₃₁H₃₀Cl₂FNO₃

2114339-57-8

Room temperature in continental US; may vary elsewhere.

DMSO : 83.33 mg/mL (150.28 mM; ultrasonic and warming and heat to 60°C)

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。-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: ≥ 8.33 mg/mL (15.02 mM); Clear solution

  此方案可获得 ≥ 8.33 mg/mL (15.02 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 83.3 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: ≥ 8.33 mg/mL (15.02 mM); Clear solution

  此方案可获得 ≥ 8.33 mg/mL (15.02 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 83.3 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: ≥ 8.33 mg/mL (15.02 mM); Clear solution

  此方案可获得 ≥ 8.33 mg/mL (15.02 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 83.3 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. El-Ahmad Y, et al. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer. J Med Chem. 2019 Nov 27.

  [2]. Monsif Bouaboula, et al. Abstract 943: SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust antitumor efficacy and limited cross-resistance in ER⁺ breast cancer.