LEE011 succinate hydrate

• CAT Number: I001445
• CAS Number: 1374639-79-8
• Molecular Formula: C27H38N8O6
• Molecular Weight: 570.64
• 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 succinate hydrate
• Target: Cyclin-Dependent Kinases
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• IC50: 307 ± 68 nM (neuroblastoma-derived cell lines)
• IUPAC Name: butanedioic acid;7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide;hydrate
• InChI: InChI=1S/C23H30N8O.C4H6O4.H2O/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;5-3(6)1-2-4(7)8;/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28);1-2H2,(H,5,6)(H,7,8);1H2
• InChIKey: PZJOFPMHNJJJSC-UHFFFAOYSA-N
• SMILES: CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5.C(CC(=O)O)C(=O)O.O

LEE011 Succinate Hydrate (also known as Ribociclib)（Cat No.:I001445）is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which are key regulators of the cell cycle. By inhibiting CDK4/6 activity, LEE011 blocks the progression of the cell cycle from the G1 to the S phase, leading to cell cycle arrest and inhibiting the proliferation of cancer cells. This compound is widely used in cancer research and is a key therapeutic agent in the treatment of hormone receptor-positive breast cancer, often used in combination with hormone therapies for enhanced efficacy.

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.