Ribociclib hydrochloride is a highly specific CDK4/6 inhibitor (IC50: 10 nM and 39 nM, respectively). It is over 1,000-fold less potent against the cyclin B/CDK1 complex.

CDK6:39 nM, CDK4:10 nM

Ribociclib hydrochloride treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition results in 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 (200 mg/kg) daily for 21 days significantly delays tumor growth in CB17 immunodeficient mice bearing BE2C or NB-1643 (MYCN amplified, sensitive in vitro) xenografts, with notable effects observed through the treatment period (p<0.0001 for both). However, tumor growth resumes after cessation of treatment. The regimen, also applied to EBC1 (non-amplified, resistant in vitro) xenografts for comparison, demonstrates a favorable safety profile across all xenograft models, indicated by the absence of weight loss or toxicity signs [2].