LEE-011


Catalog No. size PriceQuantity
M6672-2 2mg solid $75
M6672-10 10mg solid $324

Description

Cas:1211441-98-3 (free base)

Product Information

LEE0-11 is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. 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.

 

Chemical Formula: C23H30N8O

 

Exact Mass: 434.25426

 

Molecular Weight: 434.54 

 

Elemental Analysis: C, 63.57; H, 6.96; N, 25.79; O, 3.68

 

Synonym: 

 

LEE011

LEE-011

LEE 011

Ribociclib

Kisqali

 

Chemical Name:

7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

 

InChi Key:

RHXHGRAEPCAFML-UHFFFAOYSA-N

 

InChi Code:  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)

 

Smiles Code:

O=C(C1=CC2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5)N(C)C

 

 

Technical Data:

 

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life:>2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro

Treating a panel of 17 neuroblastoma cell lines with Ribociclib (LEE011) across a four-log dose range (10 to 10,000 nM). Treatment with Ribociclib significantly inhibits substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines examined (mean IC50=306±68 nM, considering sensitive lines only, where sensitivity is defined as an IC50 of less than 1 μM. Ribociclib treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition results in a dose-dependent accumulation of cells in the G0/G1 phase of the cell cycle. This G0/G1 arrest becomes significant at Ribociclib concentrations of 100 nM (p=0.007) and 250 nM (p=0.01), respectively.

 

In Vivo

CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts are treated once daily for 21 days with LEE0-11 (Ribociclib; 200 mg/kg) or with a vehicle control. This dosing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of the xenograft models. Tumor growth is significantly delayed throughout the 21 days of treatment in mice harboring the BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment.

 

 

References

 

  1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548818/ PubMed PMID: 31644125.

 

  1. Bellet M, Ahmad F, Villanueva R, Valdivia C, Palomino-Doza J, Ruiz A, Gonzalez X, Adrover E, Azaro A, Valls-Margarit M, Parra JL, Aguilar J, Vidal M, Martin A, GavilaJ, Escriva-de-Romani S, Perello A, Hernando C, Lahuerta A, Zamora P, Reyes V, Alcalde M, Masanas H, Celiz P, Ruiz I, Gil M, Segui MA, de la Pena L. Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication. Ther Adv Med Oncol. 2019 May 10;11:1758835919833867. doi: 10.1177/1758835919833867. eCollection 2019. Review. PubMed PMID: 31205497; PubMed Central PMCID: PMC6535716.

 

  1. Poratti M, Marzaro G. Third-generation CDK inhibitors: A review on the synthesis and binding modes of Palbociclib, Ribociclib and Abemaciclib. Eur J Med Chem. 2019 Jun 15;172:143-153. doi: 10.1016/j.ejmech.2019.03.064. Epub 2019 Apr 4. Review. PubMed PMID: 30978559.

 

  1. Eggersmann TK, Degenhardt T, Gluz O, Wuerstlein R, Harbeck N. CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. BioDrugs. 2019 Apr;33(2):125-135. doi: 10.1007/s40259-019-00337-6. Review. PubMed PMID: 30847853.

 

  1. Petrelli F, Ghidini A, Pedersini R, Cabiddu M, Borgonovo K, Parati MC, Ghilardi M, Amoroso V, Berruti A, Barni S. Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials. Breast Cancer Res Treat. 2019 Apr;174(3):597-604. doi: 10.1007/s10549-019-05133-y. Epub 2019 Jan 18. Review. PubMed PMID: 30659432.

 

Products are for research use only. Not for human use.

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