LEE011 hydrochloride

• CAT Number: I000793
• CAS Number: 1211443-80-9
• Molecular Formula: C23H31ClN8O
• Molecular Weight: 471.00
• Purity: ≥95%
• Synonyms: (E)-7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)imino)-3,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride
• Target: Cyclin-Dependent Kinases
• Solubility: 10 mM in DMSO
• Storage: Store at -20℃
• IC50: 307 ± 68 nM (neuroblastoma-derived cell lines)
• IUPAC Name: 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide;hydrochloride
• InChI: InChI=1S/C23H30N8O.ClH/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30;/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28);1H Create Date: 2012-11-30
• InChIKey: JZRSIQPIKASMEV-UHFFFAOYSA-N
• SMILES: CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5.Cl

LEE011 hydrochloride (also known as Ribociclib)（Cat No.:I000793）is a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor used in cancer treatment, particularly in hormone receptor-positive, HER2-negative breast cancer. By inhibiting CDK4/6, LEE011 prevents the phosphorylation of the retinoblastoma (Rb) protein, leading to cell cycle arrest in the G1 phase and halting cancer cell proliferation. It is commonly used in combination with hormone therapies, such as aromatase inhibitors, to enhance therapeutic effects. LEE011 hydrochloride’s ability to target CDK4/6 makes it a promising treatment in cancers driven by cell cycle dysregulation.

Reference

[1]. Rader J, et al. Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res. 2013 Oct 28.
Abstract
PURPOSE: Neuroblastoma is a pediatric cancer that continues to exact significant morbidity and mortality. Recently, a number of cell-cycle proteins, particularly those within the Cyclin D/CDK4/CDK6/RB network, have been shown to exert oncogenic roles in neuroblastoma, suggesting that their therapeutic exploitation might improve patient outcomes. Experimental Procedures: We evaluated the effect of dual CDK4/CDK6 inhibition on neuroblastoma viability using LEE011 (Novartis Oncology), a highly specific CDK4/6 inhibitor. RESULTS: 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. In addition, 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. Although our data indicate that neuroblastomas sensitive to LEE011 were more likely to contain genomic amplification of MYCN (P = 0.01), the identification of additional clinically accessible biomarkers is of high importance. CONCLUSIONS: Taken together, our data show that LEE011 is active in a large subset of neuroblastoma cell line and xenograft models, and supports the clinical development of this CDK4/6 inhibitor as a therapy for patients with this disease. Clin Cancer Res; 19(22); 6173-82. ?2013 AACR.