LEE011 (Ribociclib)

CatalogusnummerS7440 Batch:S744003

Afdrukken

Technische gegevens

Formule

C23H30N8O
Moleculair gewicht 434.54 CAS-nr. 1211441-98-3
Oplosbaarheid (25°C)* In vitro DMSO 20 mg/mL (46.02 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Voeg oplosmiddelen afzonderlijk en in volgorde toe aan het product.)
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.
* <1 mg/ml betekent licht oplosbaar of onoplosbaar.
* Houd er rekening mee dat Selleck de oplosbaarheid van alle verbindingen intern test en de werkelijke oplosbaarheid enigszins kan afwijken van gepubliceerde waarden. Dit is normaal en is te wijten aan lichte batch-tot-batch variaties.
* Verzending op kamertemperatuur (Stabiliteitstests tonen aan dat dit product zonder koelmaatregelen kan worden verzonden.)

Voorbereiden van stamoplossingen

Biologische activiteit

Beschrijving Ribociclib is een oraal beschikbare en zeer specifieke remmer van CDK4 en CDK6 met IC50 van 10 nM en 39 nM. Fase 3.
Doelen
CDK4
(Cell-free assay)		 CDK6
(Cell-free assay)
10 nM 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 primair 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 de BE2C- of 1643-xenografts zonder gewichtsverlies of andere tekenen van toxiciteit.

Kenmerken Oraal biologisch beschikbare CDK4/6-selectieve remmer die is getest in fase III klinische proeven voor de behandeling van gevorderde borstkanker.

Protocol (uit referentie)

Celassay:

[1]
  • Cellijnen

    BE2C, IMR5, 1643, SY5Y, CHP134, SKNSH, NGP, KELLY, LAN5, NLF, NB69, SKNDZ, NBSD, NBLS, SKNFI, EBC1, SKNAS, NB16, RPE1 cell lines.

  • Concentraties

    10 μM

  • Incubatietijd

    ~100 hours

  • Methode

    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.
Dierstudie:

[1]
  • Dierlijke modellen

    Mice bearing BE2C, NB-1643, or EBC1 xenografts.

  • Doseringen

    ~200 mg/kg daily

  • Toediening

    p.o.

Referenties

  • https://pubmed.ncbi.nlm.nih.gov/24045179/
  • https://pubmed.ncbi.nlm.nih.gov/31482107/

Klantproductvalidatie

<p>Analysis of apoptosis in leukemia cells induced by LEE011. Annexin V staining of cells following 48-h treatment with LEE011 at 2 or 5 µM compared with DMSO controls. Following 5-µM LEE011 treatment, the K562 apoptotic cell percentage was 5.9 ± 0.75 vs. 1.2 ± 0.66% for the DMSO group, P = 0.001; in MV4-11 cells, the apoptotic cell percentage was 24.2 ± 3.06 vs. 0.53 ± 0.40% for the DMSO group, P = 0.005; in U937 cells, the apoptotic cell percentage was 9.9 ± 2.81 vs. 0.57 ± 0.42% for the DMSO group, P = 0.027; in HL-60 cells, the apoptotic cell percentage was 28.23 ± 6.01 vs. 0.9 ± 0.8% for the DMSO group, P = 0.015; in THP-1 cells, the apoptotic cell percentage was 1.76 ± 0.4 vs. 1.56 ± 0.45% for the DMSO group, P = 0.59; in CCRF cells, the apoptotic cell percentage was 13.77 ± 3.16 vs. 1.2 ± 0.36% for the DMSO group, P = 0.019; in NB4 cells, the apoptotic cell percentage was 12.1 ± 1.35 vs. 0.86 ± 0.25% for the DMSO group, P = 0.004; and in SHI-1 cells the apoptotic cell percentage was 12.6 ± 2.81 vs. 1.87 ± 0.75% for the DMSO group, P = 0.017. These analyses were repeated three times. *P < 0.05; **P < 0.01</p>

, , Cancer Cell Int, 2017, 17:35

IB analysis of whole cell lysates derived from mouse CT26 or 4T1 tumor cell lines treated with or without the CDK4/6 inhibitor, ribociclib.

Gegevens van [ , , Nature, 2017, 553(7686):91-95 ]

The combination of a different mTOR inhibitor temsirolimus (4 μM) and a different CDK4/6 inhibitor ribociclib (4 μM) is also synergistic against GICs (***P < 0.0001; one-way ANOVA with post-hoc Tukey analysis).

Gegevens van [ , , Clin Cancer Res, 2017, 23(22):6958-6968 ]

The effects of the CDK inhibitor abemaciclib, palbociclib, and ribociclib on Trop2 ICD cleavage. CDK inhibitors decreased Trop2 ICD abundance after the second day of CDK inhibitor treatment.

Gegevens van [ , , Cancer Res, 2016, 76(22):6723-6734 ]

Sellecks LEE011 (Ribociclib) Is geciteerd door 116 Publicaties

Cellular interactions within the immune microenvironment underpins resistance to cell cycle inhibition in breast cancers [ Nat Commun, 2025, 16(1):2132] PubMed: 40032842
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer [ Cell Rep Med, 2025, S2666-3791(25)00231-9] PubMed: 40449480
Resistance to CDK7 inhibitors directed by acquired mutation of a conserved residue in cancer cells [ EMBO J, 2025, 10.1038/s44318-025-00554-6] PubMed: 40921851
Blocking cancer-fibroblast mutualism inhibits proliferation of endocrine therapy resistant breast cancer [ Mol Syst Biol, 2025, 10.1038/s44320-025-00104-6] PubMed: 40341770
Gene expression analysis in circulating tumour cells to determine resistance to CDK4/6 inhibitors plus endocrine therapy in HR + /HER2- metastatic breast cancer patients [ J Transl Med, 2025, 23(1):400] PubMed: 40186268
Efficacy of CDK4/6 Inhibition in colorectal cancer and the role of p16 expression in predicting drug resistance [ Cell Oncol (Dordr), 2025, 10.1007/s13402-025-01080-7] PubMed: 40522623
FLT4 activation promotes acute lymphoid leukemia survival through stabilization of MDM2/MDMX and inactivation of p53 [ Oncogenesis, 2025, 14(1):14] PubMed: 40316529
Preclinical Evaluation of the Efficacy of a Cyclin-dependent Kinase Inhibitor Ribociclib in Combination with Letrozole Against Patient-Derived Glioblastoma Cells [ Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-25-0277] PubMed: 40994426
Investigation of ribociclib, abemaciclib and palbociclib resistance in ER+ breast cancer cells reveal potential therapeutic opportunities` [ Sci Rep, 2025, 15(1):28579] PubMed: 40764324
Bacterial ubiquitin ligase engineered for small molecule and protein target identification [ bioRxiv, 2025, 2025.03.20.644192] PubMed: 40166235

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NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.