Free shipping on all orders over $ 500

LEE011

Cat. No. M2218

LEE011 Structure
Size Price Availability Quantity
5mg USD 80 In stock
10mg USD 120 In stock
50mg USD 250 In stock
100mg USD 450 In stock
Bulk Inquiry?

Quality Control
Biological Activity

LEE011 is an orally available, small-molecule inhibitor of cyclin-dependent kinases (CDK) which 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. 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. 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 is currently in Phase I development by Novartis.

Protocol
Cell Experiment
Cell lines MYCN amplified neuroblastoma cell lines
Preparation method Pharmacologic growth inhibition LEE011 was provided by Novartis pharmaceuticals. A panel of neuroblastoma cell lines, selected based upon prior demonstration of substrate adherent growth, was plated in triplicate on the Xcelligence Real-Time Cell Electronic Sensing system (ACEA Biosciences) and treated 24 hours later with a four-log dose range of inhibitor or with a DMSO control. Cell indexes were monitored continuously for ~100 hours, and IC50 values were determined as follows: Growth curves were generated by plotting the cell index as a function of time and were 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 post-treatment was then calculated using a baseline area of 1 (the cell index at the time of treatment). Areas were normalized to the DMSO control, and the resulting data were analyzed using a non-linear log inhibitor vs. normalized response function (Graphpad). All experiments were repeated at least once.
Concentrations 0~10µM
Incubation time 96h
Animal Experiment
Animal models BE2C, NB-1643, or EBC1 cell line-derived xenografts of CB17 SCID−/− mice
Formulation 0.5 % methylcellulose
Dosages 200 mg/kg
Administration oral
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 434.54
Formula C23H30N8O
CAS Number 1211441-98-3
Purity 99.02%
Solubility DMSO
Storage at -20°C
References

Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma.
Rader J, et al. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. PMID: 24045179.

Related CDK Products
NU2058

NU2058 is a guanine-based CDK inhibitor with IC50 of 17 μM and 26 μM for CDK2 and CDK1.

LDC000067

LDC000067 is a highly selective CDK9 inhibitor with IC50 of 44 nM, 55/125/210/ >227/ >227-fold selectivity over CDK2/1/4/6/7.

RO-3306

RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.

LDC4297

LDC4297 is a novel CDK7 inhibitor (IC50=0.13±0.06 nM for CDK7 versus IC50s between 10 nM and 10,000 nM for all other analyzed CDKs).

THZ1

THZ1 is a covalent CDK7 inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.

  Catalog
Abmole Inhibitor Catalog 2017




Keywords: LEE011 supplier, CDK, inhibitors

Contact Us
  • Tel: +1-800-660-8580
  • Email: sales@abmole.com
  • Tel: +32 (0)2 738 09 61
  • Email: eu.order@abmole.com

Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.