LY2835219 is an effective and specific CDK4/6 inhibitor (IC50: 2/10 nM).

LY2835219 reduces cell viability with the IC50 values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells[1]. LY2835219 shows inhibition on A375R1-4, M14R, and SH4R with EC50 values ranging from 0.3 to 0.6 μM; LY2835219 inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC50 values of 395, 260, and 463 nM, respectively[2]. LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells[3].

LY2835219 (45 mg/kg, p.o.) in combination with everolimus causes a cooperative antitumor effect in HNSCC xenograft tumor[1]. LY2835219 (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model[2].

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.

1231929-97-7

C27H32F2N8

506.59

CDK4/6 dual inhibitor;LY2835219;Abemaciclib

[1]Ku B M , Yi S Y , Koh J , et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma[J]. Oncotarget, 2016, 7(12):14803-14813. [2]Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63. [3]Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37.

[1]Ni J, Kabraji S, Xie S, et al. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications. 2022, 13(1): 1-8. [2]Liu X, Hu Q, Wang W, et al. A protein-fragment complementation assay reveals that celastrol and gambogic acid suppress ERα mutants in breast cancer. Biochemical Pharmacology. 2021, 188: 114583.

Ethanol:5.06mg/mL (10mM)
DMSO:10mg/mL(19.74mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years