T025

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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。

T025 is an orally active and highly potent inhibitor of Cdc2-like kinase (CLKs), with Kd values of4.8, 0.096, 6.5, 0.61, 0.074, 1.5 and 32 nM for CLK1, CLK2, CLK3, CLK4, DYRK1A, DYRK1B and DYRK2, respectively. T025 induces caspase-3/7-mediated cell apoptosis. T025 reduces CLK-dependent phosphorylation. T025 exerts anti-proliferative activities in both hematological and solid cancer cell lines (IC50 values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research.

T025 (0-1000 nM; 72 hours) significantly suppresses the growth of MDA-MB-468 cells in a dose-dependent manner.T025 (0-1000 nM; 6 hours) reduces phosphorylation levels in MDA-MB-468 cells.Cell Viability AssayCell 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 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.

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. 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 .Animal Model:Balb/c nude mice (7 to 8 week-old females) 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) 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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Cell Cycle/DNA Damage

CDK

CDK

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2407433-00-3

382.42

C21H18N8

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 8.25 mg/mL (21.57 mM; 超声助溶 )

CNc1nc(NCc2ncccn2)c2c(c[nH]c2n1)-c1ccc2ncccc2c1

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(-20℃)

With Ice Pack

≥ 2 years