SD-36 是一种有效的STAT3PROTAC 降解剂 (Kd=~50 nM)，与其他 STAT 成员相比具有很高的选择性。SD-36 有效降解细胞中突变的 STAT3 蛋白，并抑制 STAT3 的转录活性 (IC50=10 nM)。SD-36 发挥强大的抗肿瘤活性，并在小鼠肿瘤模型中实现了完整而持久的肿瘤消退。SD-36 由 STAT3 抑制剂 SI-109、 linker 和一个用于 E3 泛素连接酶的Cereblon配体Lenalidomide类似物组成。
| 生物活性 | SD-36 is a potent and efficaciousSTAT3PROTACdegrader (Kd=~50 nM), and demonstrates high selectivity over otherSTATmembers. SD-36 also effectively degrades mutatedSTAT3proteins in cells and suppresses the transcriptional activity ofSTAT3(IC50=10 nM). SD-36 exerts robust anti-tumor activity, and achieves complete and long-lasting tumor regression in mouse tumor models. SD-36 is composed of theSTAT3 inhibitorSI-109, a linker, and an analog ofCereblonligandLenalidomidefor E3 ubiquitin ligase[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis[1].
SD-36 (0.005-5 μM; 4 days) demonstrates potent activity (IC50＜2 μM) in MOLM-16, DEL, Karpas-299, KI-JK, SU-DHL-I, SUP-M2 cell lines[1].
SD-36 (1 μM; 5 hours) completely depletes both monomeric and dimeric STAT3 protein in MOLM-16 cells[1].
Cell Viability Assay[1] | Cell Line: | MOLM-16, DEL, Karpas-299, KI-JK, SU-DHL-I, SUP-M2 cell lines | | Concentration: | 0.005, 0.05, 0.5, 5 μM | | Incubation Time: | 4 days | | Result: | Demonstrated potent activity (IC50＜2 μM) in those cell lines. |
Western Blot Analysis[1] | Cell Line: | MOLM-16 cells | | Concentration: | 1 μM | | Incubation Time: | 5 hours | | Result: | Completely depletes both monomeric and dimeric STAT3 protein. |
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体内研究
(In Vivo) | SD-36 (25-100 mg/kg; i.v.; weekly dosing for 4 weeks) achieves complete and long-lasting tumor regression in mice[1].
SD-36 effectively inhibits tumor growth at 25 and 50 mg/kg administered on day 1, 3, and 5 per week and achieved complete tumor regression at 100 mg/kg with the same schedule in the SU-DHL-1 xenograft model[1].
SD-36 at 50 mg/kg 3 times per week completely inhibits tumor growth in the SUP-M2 tumor model[1].
| Animal Model: | SCID female mice (MOLM-16 xenograft model)[1] | | Dosage: | 25, 50, 100 mg/kg | | Administration: | i.v.; weekly dosing for 4 weeks | | Result: | At 25 and 50 mg/kg weekly dosing for 4 weeks effectively inhibited tumor growth. At either 100 mg/kg weekly or 50 mg/kg twice weekly for 4 weeks induced complete tumor regression. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 150 mg/mL(129.52 mM;Need ultrasonic) 配制储备液 | 1 mM | 0.8634 mL | 4.3172 mL | 8.6345 mL | | 5 mM | 0.1727 mL | 0.8634 mL | 1.7269 mL | | 10 mM | 0.0863 mL | 0.4317 mL | 0.8634 mL |
*请根据半岛bd体育手机客户端
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半岛bd体育手机客户端
失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-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: ≥ 5 mg/mL (4.32 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (4.32 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 50.0 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%corn oil Solubility: ≥ 5 mg/mL (4.32 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (4.32 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 50.0 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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