T025 is an orally active and highly potent inhibitor of Cdc2-like kinase (CLKs) , with K d values of 4.8, 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 ( IC 50 values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research
In Vitro
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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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 AnalysisCell Line: MDA-MB-468 cells Concentration: 0, 10, 30, 100, 300 and 1000 nM Incubation Time: 6 hours Result: Decreased both pCLK2 and CLK2.
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 . 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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.
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)
