Ribociclib succinate (LEE011 succinate) is a highly specific CDK4/6 inhibitor with IC50 values of 10 nM and 39 nM, respectively, and exhibits over 1,000-fold reduced potency against the cyclin B/CDK1 complex.

CDK6:39 nM, CDK4:10 nM

Ribociclib succinate treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition causes 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. Treatment with Ribociclib obviously 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. Treating a panel of 17 neuroblastoma cell lines with Ribociclib across a four-log dose range (10 to 10,000 nM) [2].

Tumor growth is significantly delayed during 21 days of Ribociclib (LEE011; 200 mg/kg) treatment in mice with BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment. CB17 immunodeficient mice with BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts received daily treatment with Ribociclib or vehicle control, with no observed weight loss or toxicity signs in any models [2].