Abemaciclib (LY2835219) is a dual inhibitor of CDK4/6 (IC50=2/10 nM) with selectivity and specificity. Abemaciclib has antitumor activity and is used to treat advanced or metastatic breast cancer.

CDK6:10 nM, CDK4:2 nM

方法：HNSCC 细胞系 OSC-19、FaDu 和 YD-10B 用 Abemaciclib (0.01-10 μM) 处理 72 h，使用 Cell Counting Kit 检测细胞活力。
结果：Abemaciclib 处理降低了 HNSCC 细胞的细胞活力，IC50值范围为 0.5 μM 至 0.7 μM。[1]
方法：AML 细胞 MV4-11 用 Abemaciclib (0.04-5 μM) 处理 24 h，使用 Flow Cytometry 检测细胞周期情况。
结果：Abemaciclib 诱导 MV4-11 细胞的 G1 期阻滞。当浓度 ≥320 nmol/L 时，G1 期阻滞最大。[2]

方法：为检测体内抗肿瘤活性，将 Abemaciclib (45-90 mg/kg in 1% HEC in 20 mM phosphate buffer (pH2.0)) 灌胃给药给携带人舌鳞癌肿瘤 OSC-19 的 BALB/c 小鼠，每天一次，持续十四天。
结果：Abemaciclib 在治疗过程中显著降低了 OSC-19 异种移植物的肿瘤生长。Abemaciclib 处理降低了 AKT 的磷酸化，但对 mTOR 的激活没有影响。[1]
方法：为检测体内抗肿瘤活性，将 Abemaciclib (22.5-90 mg/kg in 1% HEC in 25 mmol/L PB pH2) 灌胃给药给携带黑色素瘤 A375 的 athymic nude 小鼠，每天一次，持续二十一天。
结果：Abemaciclib 在 45 或 90 mg/kg 给药方案下观察到统计学上显著的肿瘤生长抑制作用。Abemaciclib 治疗显著降低了 pS780-Rb 和 pS10-Histone H3 水平，表明 CDK4/6 抑制导致细胞周期抑制和肿瘤细胞增殖减少。[3]

Cells (5×103) are plated in 96 well plates. Cells are treated the next day for 24 to 48 hours and then assessed for caspase-3 activity by Caspase-Glo-3/7 Assay, as per manufacturer's instructions and a luminescence plate reader.

LY2835219 is dissolved in DMSO to a 10 mM concentration.? Cells are seeded in a 96-well plate, allowed to adhere overnight, and treated with DMSO control (0.1% v/v) or the indicated compounds for 72 h. Cell viability and proliferation are determined using a Cell Counting Kit according to the manufacturer's instructions. The interaction between LY2835219 and mTOR inhibitor is determined using CompuSyn. Combination index (CI) values of 1 indicates and additive drug interaction, whereas a CI of <1 is synergistic and a CI of >1 is antagonistic.