Unesbulin (PTC596) 是一种口服有效和选择性的 B 细胞特异性莫洛尼氏鼠白血病病毒整合位点 1 (BMI-1) 抑制剂。Unesbulin 在急性髓细胞白血病 (AML) 细胞中可下调 MCL-1 并诱导不依赖 p53 的线粒体凋亡。Unesbulin 具有抗白血病作用。
| 生物活性 | Unesbulin (PTC596) is an orally active and selective B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) inhibitor. Unesbulin downregulatesMCL-1and induces p53-independent mitochondrialapoptosisin acute myeloid leukemia (AML) cells. Unesbulin has anti-leukemic activity[1][2]. |
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体外研究
(In Vitro) | Unesbulin (PTC596; 20-200 nM; for 48 hours) induces apoptosis in AML cells in a p53-independent manner. BMI-1 overexpression desensitizes AML cells to PTC596-induced apoptosis[1].
Unesbulin (200 nM; for 10 hours) leads to an accumulation of cells in G2/M phase[1].
Unesbulin (0.012-1 μM; for 20 hours) significantly reduces protein levels of BMI-1[1].
Unesbulin inhibits APC/CCDC20 activity resulting in the persistent activation of CDK1 and CDK2 which mediate the hyperphosphorylation of BMI1[2].
Apoptosis Analysis[1] | Cell Line: | AML cell lines (MOLM-13, OCI-AML3, MOLM-14, MV4-11, U-937, HL-60) | | Concentration: | 20, 50, 100, 200 nM | | Incubation Time: | For 48 hours | | Result: | Induced apoptosis in a dose- and time-dependent manner with the average IC50and ED50values among six cell lines were 30.7 nM and 60.3 nM, respectively. |
Cell Cycle Analysis[1] | Cell Line: | MOLM-13 and U-937 cells | | Concentration: | 200 nM | | Incubation Time: | For 10 hours | | Result: | Led to an accumulation of cells in G2/M phase, whereas the percentage of cells in G1 phase decreased. |
Western Blot Analysis[1] | Cell Line: | MOLM-13 cell | | Concentration: | 0.012, 0.037, 0.11, 0.33, 1 μM | | Incubation Time: | For 20 hours | | Result: | Significantly reduced protein levels of BMI-1 and its downstream target ubiquitinated histone H2A.
Increased cyclin B1 and securin levels. |
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体内研究
(In Vivo) | Unesbulin (PTC596; 5 mg/kg; oral gavage; every 3 days for 13 days) significantly prolongs mouse survival[1].
Unesbulin (20 mg/kg; oral gavage; once a week for 15 days) causes tumor volume significantly smaller than that of control SCID mice with K562 cells[1].
Unesbulin (10 or 12.5 mg/kg; oral gavage; twice a week until death) causes the survival significantly longer than the vehicle-treated group in NOD-SCID mice with HL-60 cells[1].
| Animal Model: | NOD-SCID/IL2Rγ-KO (NSG) mice with MOLM-13 cells[1] | | Dosage: | 5 mg/kg | | Administration: | Oral gavage; every 3 days for 13 days | | Result: | Significantly prolonged mouse survival compared with the vehicle-treated mice in a dose-dependent manner. |
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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 : 16.67 mg/mL(39.66 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3790 mL | 11.8951 mL | 23.7903 mL | | 5 mM | 0.4758 mL | 2.3790 mL | 4.7581 mL | | 10 mM | 0.2379 mL | 1.1895 mL | 2.3790 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 ≥ 1.67 mg/mL (3.97 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 1.67 mg/mL (3.97 mM); Clear solution
此方案可获得 ≥ 1.67 mg/mL (3.97 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。 *以上所有助溶剂都可在本网站选购。
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