LEE011 is an orally available, and highly specific CDK4/6 inhibitor (IC50：10/39 nM).

LEE011（200 mg/kg/day,p.o.）明显延缓小鼠中BE2C 或者 1643细胞的生长,且无体重减轻或者其它的毒性症状.

LEE011可抑制神经细胞瘤细胞的生长,该作用受到G1细胞周期阻滞和细胞衰老的调控。LEE011对17种神经细胞瘤中的12种均有显著的生长抑制作用（平均IC50：307 nM）。

Enzyme assays are performed using a homogeneous time-resolved fluorescence assay with recombinant epitope tagged kinase domains (JAK1, 837-1142; JAK2, 828-1132; JAK3, 718-1124; Tyk2, 873-1187) or full-length enzyme (cMET and Chk2) and peptide substrate. Each enzyme reaction is performed with or without test compound (11-point dilution), JAK, cMET, or Chk2 enzyme, 500 nM (100 nM for Chk2) peptide, ATP (at the Km specific for each kinase or 1 mM), and 2.0% DMSO in assay buffer. The calculated IC50 value is the compound concentration required for inhibition of 50% of the fluorescent signal. Additional kinase assays are performed at Cerep using standard conditions at 200 nM. Enzymes tested included: Abl, Akt1, AurA, AurB, CDC2, CDK2, CDK4, CHK2, c-kit, EGFR, EphB4, ERK1, ERK2, FLT-1, HER2, IGF1R, IKKα, IKKβ, JNK1, Lck, MEK1, p38α, p70S6K, PKA, PKCα, Src, and ZAP70[1].

A panel of neuroblastoma cell lines, selected based upon prior demonstration of substrate adherent growth, is plated in triplicate on the Xcelligence Real-Time Cell Electronic Sensing system and treated 24 hours later with a four-log dose range of inhibitor or with a dimethyl sulfoxide (DMSO) control. Cell indexes are monitored continuously for ~100 hours, and IC50 values are determined as follows: growth curves are generated by plotting the cell index as a function of time and are normalized to the cell index at the time of treatment for a baseline cell index of 1. The area under the normalized growth curve from the time of treatment to 96 hours posttreatment is then calculated using a baseline area of 1 (the cell index at the time of treatment). Areas are normalized to the DMSO control, and the resulting data are analyzed using a nonlinear log inhibitor versus normalized response function. All experiments are repeated at least once. (Only for Reference)

1211441-98-3

C23H30N8O

434.54

LEE011;瑞博西尼;Ribociclib

[1]Ou J, Li H, Qiu P, et al. CDK9 modulates circadian clock by attenuating REV-ERBα activity[J]. Biochemical and biophysical research communications. 2019 Jun 11;513(4):967-973. [2]Rader J, et al. Clin Cancer Res. 2013, 19(22), 6173-6182.

[1]Ou J, Li H, Qiu P, et al. CDK9 modulates circadian clock by attenuating REV-ERBα activity. Biochemical and Biophysical Research Communications. 2019 Jun 11;513(4):967-973

DMSO:7 mg/mL (16.1 mM)
Ethanol:<1 mg/mL
H2O:<1 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years