Ribociclib; LEE 011; LEE-011 CAS 1211441-98-3 LEE011是口服活性的周期蛋白依赖性激酶（CDK）抑制剂，靶向cyclin D1/CDK4和cyclin D3/CDK6。 LEE011的生物活性 LEE011 is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. IC50 Value: 307 ± 68 nM (neuroblastoma-derived cell lines) [1] Target: CDK4;CDK6 in vitro: CDK4/6 inhibitor LEE011 specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.Treatment with LEE011 significantly reduced proliferation in 12 of 17 human neuroblastoma-derived cell lines by inducing cytostasis at nanomolar concentrations (mean IC50 = 307 ± 68 nmol/L in sensitive lines). LEE011 caused cell-cycle arrest and cellular senescence that was attributed to dose-dependent decreases in phosphorylated RB and FOXM1, respectively [1]. in vivo: Responsiveness of neuroblastoma xenografts to LEE011 translated to the in vivo setting in that there was a direct correlation of in vitro IC50 values with degree of subcutaneous xenograft growth delay [1].
