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Ribociclib

CAS No. : 1211441-98-3

MCE 国际站：Ribociclib

产品活性：Ribociclib (LEE011) 是一种高度特异性的 CDK4/6 抑制剂，IC₅₀ 值分别为 10 nM 和 39 nM，对 cyclin B/CDK1 复合体的活性低于其 1000 倍。

研究领域：Cell Cycle/DNA Damage

作用靶点：CDK

In Vitro: Treating a panel of 17 neuroblastoma cell lines with Ribociclib (LEE011) across a four-log dose range (10 to 10,000 nM). Treatment with Ribociclib significantly inhibits substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines examined (mean IC₅₀=306±68 nM, considering sensitive lines only, where sensitivity is defined as an IC₅₀ of less than 1 μM. Ribociclib treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition results in a dose-dependent accumulation of cells in the G₀/G₁ phase of the cell cycle. This G₀/G₁ arrest becomes significant at Ribociclib concentrations of 100 nM (p=0.007) and 250 nM (p=0.01), respectively.

In Vivo: CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts are treated once daily for 21 days with Ribociclib (LEE011; 200 mg/kg) or with a vehicle control. This dosing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of the xenograft models. Tumor growth is significantly delayed throughout the 21 days of treatment in mice harboring the BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment.

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