T025 是口服有效的Cdc2-like 激酶 (CLK)抑制剂，对 CLK1，CLK2，CLK3，CLK4，DYRK1A，DYRK1B 和 DYRK2 的Kd分别为4.8，0.096，6.5，0.61，0.074，1.5 和 32 nM。T025 诱导 caspase-3/7 介导的细胞凋亡 (apoptosis)。T025 可降低 CLK 依赖性磷酸化。T025 在血液和实体癌细胞系中均具有抗增殖活性 (IC50值：30-300 nM)。T025 具有抗肿瘤功效，主要用于MYC驱动的疾病研究。
| 生物活性 | T025 is an orally active and highly potent inhibitor ofCdc2-like kinase (CLKs), withKdvalues of 4.8, 0.096, 6.5, 0.61, 0.074, 1.5 and 32 nM for CLK1, CLK2, CLK3, CLK4, DYRK1A, DYRK1B andDYRK2, respectively. T025 induces caspase-3/7-mediated cellapoptosis. T025 reduces CLK-dependent phosphorylation. T025 exerts anti-proliferative activities in both hematological and solidcancercell lines (IC50values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research[1]. |
| IC50& Target | CLK2 0.096 nM (Kd) | CLK4 0.61 nM (Kd) | CLK1 4.8 nM (Kd) | CLK3 6.5 nM (Kd) | DYRK1A 0.074 nM (Kd) | DYRK1B 1.5 nM (Kd) | DYRK2 32 nM (Kd) |
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体外研究
(In Vitro) | T025 (0-1000 nM; 72 hours) significantly suppresses the growth of MDA-MB-468 cells in a dose-dependent manner[1].
T025 (0-1000 nM; 6 hours) reduces phosphorylation levels in MDA-MB-468 cells[1].
Cell Viability Assay[1] | Cell Line: | MDA-MB-468 cells | | Concentration: | 1, 10, 100 and 1000 nM | | Incubation Time: | 72 hours | | Result: | Resulted in concentration dependent growth inhibition. |
Western Blot Analysis[1] | Cell Line: | MDA-MB-468 cells | | Concentration: | 0, 10, 30, 100, 300 and 1000 nM | | Incubation Time: | 6 hours | | Result: | Decreased both pCLK2 and CLK2. |
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体内研究
(In Vivo) | T025 (50 mg/kg; p.o.; 2, 4, 8 hours, Balb/c nude mice (7 to 8 week-old females).) suppress the CLK-dependent phosphorylation and induce skipping exon in various genes[1].
T025 (50 mg/kg; p.o.; twice daily on 2 days per week, for 3 weeks, Balb/c nude mice (7 to 8 week-old females).) inhibits MDA-MB-468 xenograft mice tumor growth and without affect body weight[1].
| Animal Model: | Balb/c nude mice (7 to 8 week-old females)[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration; 2, 4, 8 hours. | | Result: | pCLK2 detected with immunohistochemistry and immunoblotting decreased, by a reduction in the RPS6KB1 exon 7 and BCLAF1 exon 11 percentage splice-in (PSI) values. |
| Animal Model: | Balb/c nude mice (7 to 8 week-old females)[1] | | Dosage: | 50 mg/kg | | Administration: | Oral administration; twice daily on 2 days per week, for 3 weeks. | | Result: | Suppressed tumor growth and< 10% nadir body weight loss. |
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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 : 8.25 mg/mL(21.57 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.6149 mL | 13.0746 mL | 26.1493 mL | | 5 mM | 0.5230 mL | 2.6149 mL | 5.2299 mL | | 10 mM | 0.2615 mL | 1.3075 mL | 2.6149 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。 |
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