SAR439859 (compound 43d) 是一种具有口服活性，非甾体和选择性雌激素受体降解剂 (SERD)。SAR439859 是一种有效的 ER 拮抗剂，具有 ER 降解活性，EC50为 0.2 nM。SAR439859 可在 ER+乳腺癌中表现出强大的抗肿瘤功效和有限的交叉耐药性。
| 生物活性 | SAR439859 (compound 43d) is an orally active, nonsteroidal and selectiveestrogen receptordegrader (SERD). SAR439859 is a potentERantagonist and has ER degrading activity with anEC50of 0.2 nM forERαdegradation[1]. SAR439859 demonstrates robust antitumor efficacy and limited cross-resistance in ER+breastcancer[2]. |
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体外研究
(In Vitro) | 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].
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体内研究
(In Vivo) | 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/hokg), low to moderate volume of distribution (Vss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T1/2was variable across species (1.98 h in mouse, 4.13 h in rat and 9.80 h in dog)[1].
| Animal Model: | Nu/nu mouse with MCF7 tumor xenograft model[1] | | Dosage: | 2.5, 5, 12.5, 25 mg/kg | | Administration: | Orally; twice daily for 30 days | | Result: | Exhibited substantial tumor-growth inhibition and displayed tumor regression at the dose of 25 mg/kg/BID. |
| Animal Model: | Mouse, rat and dog[1] | | Dosage: | 3 mg/kg (iv) and 10 mg/kg (po) (Pharmacokinetic Analysis) | | Administration: | Iv or po | | Result: | Showed a low to moderate clearance in the three animal species tested (0.03-1.92 L/hokg), low to moderate volume of distribution (Vss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 83.33 mg/mL(150.28 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.8035 mL | 9.0175 mL | 18.0349 mL | | 5 mM | 0.3607 mL | 1.8035 mL | 3.6070 mL | | 10 mM | 0.1803 mL | 0.9017 mL | 1.8035 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 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。 *以上所有助溶剂都可在本网站选购。
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