Ribociclib, Free Base

Soluble in DMSO. Ribociclib, also known as LEE011, is a highly specific CDK4/6 inhibitor. It significantly inhibited proliferation in 12 of 17 human neuroblastoma-derived cell lines with an average IC50 value of 307 nM in the 12 sensitive cell lines. It also caused cell-cycle arrest and cellular senescence that might be related to decreases in phosphorylated RB and FOXM1, respectively. In addition, ribociclib induced subcutaneous neuroblastoma xenograft growth delay in vivo. Rader J. et al. 'Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma.' Clin. Cancer Res. 19: 6173-6182 (2013). Ribociclib inhibited CDK4/6 kinase activity with IC50 value at the nM level and showed high selectivity for these targets. In a number of preclinical tumor models, ribociclib demonstrated anti-tumor activity that correlated with CDK4/6 inhibition. Ribociclib showed anti-tumor activity in melanoma and breast cancer models as a single agent or in combination with other agents. Kim S. et al. 'LEE011: An orally bioavailable, selective small molecule inhibitor of CDK4/6- Reactivating Rb in cancer.' Mol. Cancer Ther. 12: Abstract PR02 (2013). A Phase 1 study of ribociclib demonstrated an acceptable safety profile, dose dependent PK, and preliminary clinical activity in patients with advanced solid tumors or lymphomas. Infante J.R. et al. 'Phase 1 multicenter, open label, dose-escalation study of LEE011, an oral inhibitor of cyclin-dependent kinase 4/6, in patients with advanced solid tumors or lymphomas.' Mol. Cancer Ther. 12: Abstract A276 (2013). Related CAS numbers: 1211443-80-9 for the hydrochloride salt, 1374639-75-4 for the succinate (1:1) salt, 1374639-79-8 for the (1:1) succinate hydrate salt, whose hydration level was not specified.