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LEE011CDK4/6 inhibitor

LEE011

Catalog No. A8641
Size Price Stock Qty
10mM (in 1mL DMSO) $88.00 In stock
5mg $80.00 In stock
10mg $120.00 In stock
25mg $200.00 In stock
50mg $250.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

LEE011

Biological Activity

Description LEE011 is an orally available and highly specific inhibitor of CDK4/6.
Targets CDK4 CDK6        
IC50            

Protocol

Cell experiment [1]:

Cell lines

Neuroblastoma cell lines

Preparation method

The solubility of this compound in DMSO is >10.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

IC50: 306 ± 68 nM, 24 hours

Applications

Treatment with LEE011 significantly inhibited substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines with mean IC50 of 306 ± 68 nM. LEE011 treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition resulted in a dose-dependent accumulation of cells in the G0/G1 phase of the cell cycle.

Animal experiment [1]:

Animal models

Mice bearing BE2C, or NB-1643 xenografts

Dosage form

Oral administration, 200 mg/kg, once daily for 21 days

Application

LEE011 (200 mg/kg daily, p.o.) significantly delayed tumor growth in mice harboring the BE2C or NB-1643 xenografts with no weight loss or other signs of toxicity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Rader J A, Russell M R, Hart L S, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma[J]. Clinical cancer research, 2013, 19(22): 6173-6182.

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Chemical Properties

Cas No. 1211441-98-3 SDF Download SDF
Chemical Name 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
Canonical SMILES CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5
Formula C23H30N8O M.Wt 434.54
Solubility >10.9mg/mL in DMSO Storage Store at -20°C
General tips N/A
Shipping Condition N/A

Background

LEE011 (NVP-LEE011) is a highly specific inhibitor of CDK4/CDK6 and functions via decreasing in phosphorylated RB and FOXM1 [1]. When tested with 17 human neuroblastoma cell lines, 12 of them were sensitive to LEE011 treatment with mean IC50=306±68 nM [2].
CDK4/6 could increase G1-S phase cell cycle progression and ultimately cellular proliferation via phosphorylating tumor suppressor protein RB. CDK4/6 signaling also could senescence suppression by regulating FOXM1 transcription[3]. Numerous studies have shown that over-expression of CDK4/CDK6 correlated with tumorigenesis and disease progression [4].
LEE011 is a novel inhibitor for CDK4/CDK6. When subjected to human liposarcoma cell lines, treated with LEE011 could dramatically decrease cell growth via arresting cell cycle G0-G1 [1]. In 12 of 17 human neuroblastoma-derived cell lines, treatment with LEE011 could significantly reduce cell proliferation [2].
In a mouse model with human liposarcoma xerography, continued treating the mouse with LEE011 orally could inhibit tumor growth or induce regression without detrimental effects on mouse weight [1]. In mice xerography with neuroblastoma cells, treated with LEE011 could inhibit the tumor growth [2].
References:
1.Zhang, Y.X., et al., Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. Mol Cancer Ther, 2014. 13(9): p. 2184-93.
2.Rader, J., et al., Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res, 2013. 19(22): p. 6173-82.
3.Paternot, S., et al., The CDK4/CDK6 inhibitor PD0332991 paradoxically stabilizes activated cyclin D3-CDK4/6 complexes. Cell Cycle, 2014. 13(18): p. 2879-88.
4.Dickson, M.A., Molecular pathways: CDK4 inhibitors for cancer therapy. Clin Cancer Res, 2014. 20(13): p. 3379-83.