Name: LEE011 (Ribociclib)
Brand: Selleck Chemicals
SKU: S7440
Rating: 5 (112 reviews)

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Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Overige CDK Inhibitoren	AS2863619 Ro-3306 SEL120 (SEL120-34A) hydrochloride INX-315 Tagtociclib (PF-07104091) PF-07220060 (CDK4/6-IN-6) AZD4573 ON123300 Enitociclib (BAY 1251152) Samuraciclib (ICEC0942) hydrochloride

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	434.54	Formule	C₂₃H₃₀N₈O	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	1211441-98-3	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	LEE011			Smiles	CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5

Oplosbaarheid

In vitro
Batch:

DMSO : 8 mg/mL (18.41 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.100mg/ml (2.53mM)	Taking the 1 mL working solution as an example, add 50 μL of 22 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	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, als duale CDK4/CDK6-remmer, remt significant de groei van 12 van de 17 neuroblastoomcellijnen met een gemiddelde IC50 van 307 nM. De groeiremming van neuroblastoomcellijnen is voornamelijk cytostatisch en wordt gemedieerd door een G1 Cell Cycle arrest en cellulaire senescentie.
In vivo	LEE011 (200 mg/kg dagelijks, p.o.) veroorzaakt significant tumorgroeivertraging bij muizen met BE2C- of 1643-xenografts zonder gewichtsverlies of andere tekenen van toxiciteit.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/24045179/ [2] https://pubmed.ncbi.nlm.nih.gov/31482107/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	pRb(S807) / Rb / p53 / Cyclin E / Cyclin D1 / CDK4 / CDK6 / p27 / p21 / PARP		29789630
Growth inhibition assay	Cell viability		26390342

Informatie klinische proef

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
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

Technische ondersteuning

Gebruiksaanwijzing

Tel: +1-832-582-8158 Ext:3

Als u nog andere vragen heeft, kunt u een bericht achterlaten.

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C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

LEE011 (Ribociclib) CDK4/6 remmer

Chemische structuur

Moleculair gewicht: 434.54