CDK4/6/1 Inhibitor

CDK4/6/1 Inhibitor is a CDK4/6 inhibitor with IC50s of 3 and 1 nM, respectively.

Research Areas >> Cancer

IC50: 3 nM (CDK4), 1 nM (CDK6)[1]

CDK4/6/1 Inhibitor is a potent anti-proliferative agent that arrests U87MG cell line exclusively in G1 (IC50=15.3 ± 2.9 nM in the anti-proliferation assay). U87MG cells exposed to varying concentrations of CDK4/6/1 Inhibitor for 24 hours show a dose-related increase in G1 arrest, and a significant increase in the percentage of cells in G1 is found in as little as 13.72 nM of CDK4/6/1 Inhibitor[1].

CDK4/6/1 Inhibitor has tumor growth inhibition values ranging from 62% to 99% for doses ranging from 3.125 to 50 mg/kg in an orthotopic xenograft mouse model of glioblastoma multiforme, and no significant body weight loss is observed. The increase in life span based on the median survival time of vehicle-treated animals in mice administered a dose of 50 mg/kg is significant at 162%[1].

The U87MG glioblastoma cells are treated with CDK4/6/1 and incubated for 72 h at 37°C. Then the medium is removed, 4% paraformaldehyde (50 µL/well) is added to the wells, and the cells are fixed for 30 min at RT. Cells are washed twice with phosphate-buffered saline (PBS) solution, and permeabilized in 0.2% Triton-X100 for 5 min. Cells are ished twice with PBS, after which 50 µL DAPI (1 µg/mL) is added to the wells, followed by incubation of the cells in the dark for 20 min. After ishing three times with PBS, PBS (100 µL/well) is added to the wells. The plates are scanned using IN Cell Analyzer 2200[1].

Mice[1] In the U87MG-Luc orthotopic xenograft mouse model, mice are treated with 3.125, 6.25, 12.5, 25, 50 mg/kg QD CDK4/6/1 Inhibitor for 28 days

[1]. Yin L, et al. A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy. Eur J Med Chem. 2018 Jan 20;144:1-28.

Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | THZ531 | RO-3306 | Flavopiridol | NVP 2 | BAY-1143572 Racemate | CYC-065 | AZD5438 | BIO | Kenpaullone | SNS-032 (BMS-387032)