Ribociclib (LEE011)

• CAT Number: I000792
• CAS Number: 1211441-98-3
• Molecular Formula: C23H30N8O
• Molecular Weight: 434.54
• Purity: ≥95%
• Synonyms: Ribociclib; LEE011; 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
• Target: CDK
• Solubility: DMSO: ≥ 4.3 mg/mL, DMSO: ＜ 8.4 mg/mL
• Storage: Store at -20°C
• 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
• InChI: InChI=1S/C23H30N8O/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)
• InChIKey: RHXHGRAEPCAFML-UHFFFAOYSA-N
• SMILES: CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5

Ribociclib (LEE011)(Cat No.:I000792) is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which are enzymes that play a role in the regulation of the cell cycle. By inhibiting these enzymes, Ribociclib can help to slow or stop the growth of cancer cells. Ribociclib is typically used in combination with other drugs, such as hormonal therapies, for the treatment of hormone receptor-positive, HER2-negative advanced, or metastatic breast cancer in postmenopausal women. It may also be used in certain other types of cancer, including neuroblastoma.

Overview of Clinical Research

Ribociclib(LEE011) is an orally available cyclin-dependent kinase (CDK) 4 inhibitor as well as CDK 6 inhibitor. The phase II study for breast cancer is ongoing. 

Reference

1: Kwapisz D. Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib. Breast Cancer Res Treat. 2017 Nov;166(1):41-54. doi: 10.1007/s10549-017-4385-3. Epub 2017 Jul 24. Review. PubMed PMID: 28741274.
2: Zangardi ML, Spring LM, Blouin GC, Bardia A. Ribociclib for post-menopausal women with HR+/HER2- advanced or metastatic breast cancer. Expert Rev Clin Pharmacol. 2017 Nov;10(11):1169-1176. doi: 10.1080/17512433.2017.1376653. Epub 2017 Sep 18. Review. PubMed PMID: 28875723.
3: Costa R, Costa RB, Talamantes SM, Helenowski I, Peterson J, Kaplan J, Carneiro BA, Giles FJ, Gradishar WJ. Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib. Breast. 2017 Oct;35:1-7. doi: 10.1016/j.breast.2017.05.016. Epub 2017 Jun 12. Review. PubMed PMID: 28618307.
4: Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors. Clin Cancer Res. 2017 Jul 1;23(13):3251-3262. doi: 10.1158/1078-0432.CCR-16-3157. Epub 2017 Mar 28. Review. PubMed PMID: 28351928.
5: Curigliano G, Criscitiello C, Esposito A, Intra M, Minucci S. Pharmacokinetic drug evaluation of ribociclib for the treatment of metastatic, hormone-positive breast cancer. Expert Opin Drug Metab Toxicol. 2017 May;13(5):575-581. doi: 10.1080/17425255.2017.1318848. Epub 2017 Apr 21. Review. PubMed PMID: 28395543.
6: Barroso-Sousa R, Shapiro GI, Tolaney SM. Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Breast Care (Basel). 2016 Jun;11(3):167-73. doi: 10.1159/000447284. Epub 2016 Jun 22. Review. PubMed PMID: 27493615; PubMed Central PMCID: PMC4960359.