Ribociclib succinate hydrate is a highly specific CDK4/6 inhibitor (IC50s: 10 nM and 39 nM, respectively). It also is over 1,000-fold less potent against the cyclin B/CDK1 complex.

CDK4:10 nM, CDK6:39 nM

Ribociclib succinate hydrate 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].

Treatment with Ribociclib (LEE011; 200 mg/kg) or vehicle control for 21 days significantly delayed tumor growth in CB17 immunodeficient mice bearing BE2C or NB-1643 (MYCN amplified, sensitive in vitro) xenografts, with both groups showing a marked growth inhibition (p<0.0001); however, tumor growth resumed after the treatment period. This study also included EBC1 (non-amplified, resistant in vitro) xenografts in the treatment regimen. The daily dosing of Ribociclib was well tolerated across all xenograft models, with no observed weight loss or signs of toxicity [2].