PROTAC-O4I2 是一种靶向剪接因子 3B1 (SF3B1) 的PROTAC。PROTAC-O4I2 在 K562 细胞中诱导 FLAG-SF3B1 降解，IC50值为 0.244 μM。PROTAC-O4I2 还诱导 K562 WT 细胞凋亡 (apoptosis)。
| 生物活性 | PROTAC-O4I2 is aPROTACtargets splicing factor 3B1 (SF3B1). PROTAC-O4I2 induces FLAG-SF3B1 degradation with anIC50value of 0.244 μM in K562 cells. PROTAC-O4I2 also induces cellularapoptosisin K562 WT cells[1]. |
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体外研究
(In Vitro) | PROTAC-O4I2 introduces Thalidomide to ubiquitin E3 ligase cereblon (CRBN), which selectively degrades SF3B1 and inhibits tumor growth in cells[1].
PROTAC-O4I2 degrades and inhibits SF3B1 in K562 cells. PROTAC-O4I2 exhibits anti-proliferation effects on SF3B1 WT, SF3B1 OE, and SF3B1 K700E cells with IC50s of 228, 63, and 90 nM, respectively[1].
PROTAC-O4I2 induces FLAG-SF3B1 degradation in a concentration-dependent manner with a half maximal inhibitory concentration (IC50) value of 0.244 μM in K562 cells[1].
Cell Proliferation Assay[1] | Cell Line: | K562 control cells (WT), cells overexpressing SF3B1 (OE), and cells expressing SF3B1K700E(K700E) | | Concentration: | 1 pM, 0.1 nM, 10 nM, 1 μM, 100 μM | | Incubation Time: | 72 hours | | Result: | In K562 WT cells, the parental compound O4I2 exhibited a marginal anti-proliferation effect (IC50>10 μM). In contrast, PROTAC-O4I2 showed significantly higher toxicity with an IC50of 228 nM, nearly 3-fold less potent than pladienolide B (IC50, 76 nM). Cells overexpressing SF3B1 WT was slightly resistant to pladienolide B (IC50, 134 nM), but more sensitive to PROTAC-O4I2 (an IC50value of 63 nM). |
Apoptosis Analysis[1] | Cell Line: | K562 cell | | Concentration: | 1 μM | | Incubation Time: | 48 h | | Result: | Induced cellular apoptosis s in cells expressing SF3B1WTor SF3B1K700E. |
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体内研究
(In Vivo) | PROTAC-O4I2 (10 μM) significantly increases survival by interference with the maintenance and proliferation of tumor in aDrosophilaintestinal tumor model[1].
| Animal Model: | Drosophila melanogaster[1] | | Dosage: | 10 μM | | Administration: | Flies were fed on a round filter paper loaded with PROTAC-O4I2 in a 5% sucrose solution, maintained at 18℃ and flipped into a freshly prepared vial every 2 days | | Result: | Decreased stem cell activity, blocked the initiation and growth of tumor, and improved the survival of the Drosophila ISC tumor model. |
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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 : 250 mg/mL(410.44 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.6418 mL | 8.2088 mL | 16.4177 mL | | 5 mM | 0.3284 mL | 1.6418 mL | 3.2835 mL | | 10 mM | 0.1642 mL | 0.8209 mL | 1.6418 mL |
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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
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此方案可获得 ≥ 2.08 mg/mL (3.41 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 *以上所有助溶剂都可在本网站选购。
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