Home Cell Cycle CDK Inhibiteur LEE011 (Ribociclib)

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LEE011 (Ribociclib) inhibiteur de CDK4/6

Réf. CatalogueS7440

Le Ribociclib est un inhibiteur oralement disponible et hautement spécifique de CDK4 et CDK6 avec des IC50 de 10 nM et 39 nM. Phase 3.
LEE011 (Ribociclib) CDK Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 434.54

Aller à

Contrôle Qualité (Quality Control)

Lot : Pureté : 99.99%
99.99

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires Type d'essai Concentration Temps d'incubation Formulation Description de l'activité PMID
DFSP105 Growth Inhibition Assay 24 h GI50=276 nM 25852058
Myoblast Growth Inhibition Assay 72 h IC50=1035 nM 25810375
IMRS Growth Inhibition Assay 72 h IC50=873 nM 25810375
SKNAS Growth Inhibition Assay 72 h IC50＞10000 nM 25810375
Rh28 Growth Inhibition Assay 72 h IC50=845 nM 25810375
Rh41 Growth Inhibition Assay 72 h IC50=7187 nM 25810375
CW9019 Growth Inhibition Assay 72 h IC50=9912 nM 25810375
Rh5 Growth Inhibition Assay 72 h IC50＞10000 nM 25810375
Rh30 Growth Inhibition Assay 72 h IC50＞10000 nM 25810375
778 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
449 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
LP3 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
LP6 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
LP8 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
LPS141 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
778 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
449 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
LP3 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
LP6 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
LP8 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
LPS141 Growth Inhibition Assay 3.33 μM 24 h decreases the proportion of cells in S phase 25028469
IMR5 Growth Inhibition Assay 24 h DMSO IC50=126 nM 24045179
BE2C Growth Inhibition Assay 24 h DMSO IC50=134 nM 24045179
1643 Growth Inhibition Assay 24 h DMSO IC50=147 nM 24045179
SKNSH Growth Inhibition Assay 24 h DMSO IC50=148 nM 24045179
SY5Y Growth Inhibition Assay 24 h DMSO IC50=154 nM 24045179
NGP Growth Inhibition Assay 24 h DMSO IC50=175 nM 24045179
KELLY Growth Inhibition Assay 24 h DMSO IC50=220 nM 24045179
CHP134 Growth Inhibition Assay 24 h DMSO IC50=273 nM 24045179
NLF Growth Inhibition Assay 24 h DMSO IC50=328 nM 24045179
LAN5 Growth Inhibition Assay 24 h DMSO IC50=429 nM 24045179
NB69 Growth Inhibition Assay 24 h DMSO IC50=738 nM 24045179
SKNDZ Growth Inhibition Assay 24 h DMSO IC50=801 nM 24045179
NBSD Growth Inhibition Assay 24 h DMSO IC50=1900 nM 24045179
SKNF1 Growth Inhibition Assay 24 h DMSO IC50=3500 nM 24045179
EBC1 Growth Inhibition Assay 24 h DMSO IC50=6400 nM 24045179
SKNAS Growth Inhibition Assay 24 h DMSO IC50＞10000 nM 24045179
NB16 Growth Inhibition Assay 24 h DMSO IC50＞10000 nM 24045179
RPE1 Growth Inhibition Assay 24 h DMSO IC50＞10000 nM 24045179
Sf21 Function assay 10 mins Inhibition of recombinant human full length N-terminal GST-tagged CDK4/Cyclin-D3 co-expressed in baculovirus infected sf21 cells using Rb substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method, IC50 = 0.013 μM. 29518312
Sf21 Function assay 10 mins Inhibition of recombinant human full length C-terminal 6His-tagged CDK9/Cyclin-T1 co-expressed in baculovirus infected sf21 cells using PDKtide substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method, IC50 = 0.197 μM. 29518312
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.2862 μM. 29407975
SEM Antiproliferative assay 72 hrs Antiproliferative activity against human SEM cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.4605 μM. 29407975
KOPN8 Antiproliferative assay 72 hrs Antiproliferative activity against human KOPN8 cells after 72 hrs by CelTiter-Glo assay, EC50 = 0.5008 μM. 29407975
NCI-H1299 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H1299 cells assessed as reduction in cell viability after 72 hrs by CCK8 assay, IC50 = 5.46 μM. 29518312
T47D Growth inhibition assay 72 hrs Growth inhibition of human T47D cells incubated for 72 hrs by CCK8 assay, IC50 = 6.227 μM. 28651979
T47D Cytotoxicity assay 72 hrs Cytotoxicity against human T47D cells assessed as reduction in cell viability after 72 hrs by CCK8 assay, IC50 = 6.23 μM. 29518312
H1299 Growth inhibition assay 72 hrs Growth inhibition of human H1299 cells incubated for 72 hrs by CCK8 assay, IC50 = 7.637 μM. 28651979
KOPN8 Apoptosis assay 0.5 uM 3 hrs Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM after 3 hrs by Western blot analysis 29407975
KOPN8 Apoptosis assay 0.5 uM 24 hrs Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM pre-treated with NAC for 1 hr and measured after 24 hrs by Western blot analysis 29407975
Hep3B Cell cycle assay 24 hrs Cell cycle arrest in human Hep3B cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
HepG2 Cell cycle assay 24 hrs Cell cycle arrest in human HepG2 cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
A549 Cell cycle assay 24 hrs Cell cycle arrest in human A549 cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
NCI-H460 Cell cycle assay 24 hrs Cell cycle arrest in human NCI-H460 cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
T47D Cell cycle assay 24 hrs Cell cycle arrest in human T47D cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
MDA-MB-231 Cell cycle assay 24 hrs Cell cycle arrest in human MDA-MB-231 cells assessed as accumulation at G0/G1 phase after 24 hrs by propidium iodide staining based flow cytometry 29518312
Fluc-labeled 4T1 Antitumor assay 130 mg/kg 18 days Antitumor activity against mouse Fluc-labeled 4T1 cells implanted in Balb/c mouse assessed as reduction in tumor weight at 130 mg/kg, ip administered daily for 18 days measured after 8 to 25 days 29518312
T47D Cell cycle assay 24 hrs Induction of cell cycle arrest in human T47D cells assessed as increase in G0/G1 phase accumulation incubated for 24 hrs by flow cytometry 28651979
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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire 434.54 Formule

C23H30N8O

 Stockage (À compter de la date de réception)
N° CAS 1211441-98-3 Télécharger le SDF Stockage des solutions mères

Synonymes LEE011 Smiles CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5

Solubilité (Solubility)

In vitro
Lot:

DMSO : 8 mg/mL (18.41 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse Concentration Volume Poids moléculaire
Calculateur de dilution Calculateur de poids moléculaire

In vivo
Lot:

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

mg/kg g μL

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH2O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Caractéristiques
Orally bioavailable CDK4/6-selective inhibitor that has been tested in Phase III clinical trials for treatment of advanced breast cancer.
Targets/IC50/Ki
CDK4
(Cell-free assay)
10 nM
CDK6
(Cell-free assay)
39 nM
In vitro

LEE011, en tant qu'inhibiteur double de CDK4/CDK6, inhibe significativement la croissance de 12 des 17 lignées cellulaires de neuroblastome avec une IC50 moyenne de 307 nM. L'inhibition de la croissance des lignées cellulaires de neuroblastome est principalement cytostatique et est médiée par un arrêt du G1 Cell Cycle et une sénescence cellulaire.

In vivo

LEE011 (200 mg/kg par jour, p.o.) provoque un retard significatif de la croissance tumorale chez les souris porteuses des xénogreffes BE2C ou 1643 sans perte de poids ni autres signes de toxicité.

Références

Applications (Applications)

Méthodes Biomarqueurs Images PMID
Western blot pRb(S807) / Rb / p53 / Cyclin E / Cyclin D1 / CDK4 / CDK6 / p27 / p21 / PARP
S7440-WB1
29789630
Growth inhibition assay Cell viability
S7440-viability1
26390342

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT Recrutement Conditions Promoteur/Collaborateurs Date de début Phases
NCT05843253 Not yet recruiting
High Grade Glioma|Diffuse Intrinsic Pontine Glioma|Anaplastic Astrocytoma|Glioblastoma|Glioblastoma Multiforme|Diffuse Midline Glioma H3 K27M-Mutant|Metastatic Brain Tumor|WHO Grade III Glioma|WHO Grade IV Glioma
Nationwide Children''s Hospital|Novartis
 May 30 2024 Phase 2
NCT06075758 Recruiting
Breast Cancer
Novartis Pharmaceuticals|Novartis
 March 7 2024 --
NCT05996107 Recruiting
Breast Cancer
University of Michigan Rogel Cancer Center
 February 27 2024 Phase 1