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, CDK2-CyclinE:504 nM, GSK-3β:192 nM, PIM1:50 nM, JNK3:389 nM, CDK7-CyclinH-MAT1:3910 nM, CDK2:504 nM, CDK4:2 nM, CK2:117 nM, FLT3 (D835Y):403 nM, PIM2:3400 nM, GSK3b:192 nM, DRAK1:659 nM, FLT3:3960 nM, CDK5:355 nM, CDK5-p25:355 nM, CDK1:1627 nM, CDK9-CyclinT1:57 nM, DYRK2:61 nM, CDK1-cyclinB1:1627 nM, HIPK2:31 nM, CDK5-p35:287 nM, CDK7:3910 nM

METHODS: HNSCC cell lines OSC-19, FaDu and YD-10B were treated with Abemaciclib (0.01-10 μM) for 72 h, and cell viability was measured by Cell Counting Kit.
RESULTS: Abemaciclib treatment decreased the cell viability of HNSCC cells with IC50 values ranging from 0.5 μM to 0.7 μM. [1]
METHODS: AML cells MV4-11 were treated with Abemaciclib (0.04-5 μM) for 24 h. The cell cycle was detected using Flow Cytometry.
RESULTS: Abemaciclib induced G1 phase block in MV4-11 cells. The G1-phase block was maximized when the concentration was ≥320 nmol/L. The RESULTS showed that Abemaciclib induced G1-phase block in MV4-11 cells. [2]

METHODS: To assay antitumor activity in vivo, Abemaciclib (45-90 mg/kg in 1% HEC in 20 mM phosphate buffer (pH 2.0)) was administered by gavage to BALB/c mice bearing human tongue squamous carcinoma tumors OSC-19 once daily for fourteen days.
RESULTS: Abemaciclib significantly reduced tumor growth in OSC-19 xenografts during treatment. abemaciclib treatment decreased AKT phosphorylation but had no effect on mTOR activation. [1]
METHODS: To assay antitumor activity in vivo, Abemaciclib (22.5-90 mg/kg in 1% HEC in 25 mmol/L PB pH2) was administered by gavage to athymic nude mice harboring melanoma A375 once a day for twenty-one days.
RESULTS: Statistically significant tumor growth inhibition was observed with Abemaciclib at 45 or 90 mg/kg dosing regimens. abemaciclib treatment significantly reduced pS780-Rb and pS10-Histone H3 levels, suggesting that CDK4/6 inhibition resulted in cell cycle inhibition and reduced tumor cell proliferation. [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.

DMSO: < 1 mg/mL (insoluble or slightly soluble), Sonication is recommended.

Ethanol: 1.69 mg/mL (3.34 mM), Sonication is recommended.

10% DMSO+90% Saline: 0.1 mg/mL (0.2 mM), Solution.