LEE011 (Ribociclib)

N.º de catálogoS7440 Lote:S744005

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Datos técnicos

Fórmula

C23H30N8O
Peso molecular 434.54 Número CAS 1211441-98-3
Solubilidad (25°C)* In vitro DMSO 8 mg/mL (18.41 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Agregue los solventes al producto individualmente y en orden.)
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 significa ligeramente soluble o insoluble.
* Tenga en cuenta que Selleck prueba la solubilidad de todos los compuestos internamente, y la solubilidad real puede diferir ligeramente de los valores publicados. Esto es normal y se debe a ligeras variaciones entre lotes.
* Envío a temperatura ambiente (Las pruebas de estabilidad demuestran que este producto se puede enviar sin medidas de refrigeración.)

Preparación de soluciones madre

Actividad biológica

Descripción Ribociclib es un inhibidor oralmente disponible y altamente específico de CDK4 y CDK6 con una IC50 de 10 nM y 39 nM. Fase 3.
Objetivos
CDK4
(Cell-free assay)		 CDK6
(Cell-free assay)
10 nM 39 nM
In vitro

LEE011, como inhibidor dual de CDK4/CDK6, inhibe significativamente el crecimiento de 12 de 17 líneas celulares de neuroblastoma con una IC50 media de 307 nM. La inhibición del crecimiento de las líneas celulares de neuroblastoma es principalmente citostática y está mediada por una detención del Cell Cycle en G1 y la senescencia celular.

In vivo

LEE011 (200 mg/kg diarios, p.o.) causa un retraso significativo en el crecimiento tumoral en ratones portadores de xenoinjertos BE2C o 1643 sin pérdida de peso u otros signos de toxicidad.

Características Inhibidor selectivo de CDK4/6 biodisponible por vía oral que ha sido probado en ensayos clínicos de fase III para el tratamiento del cáncer de mama avanzado.

Protocolo (de referencia)

Ensayo celular:

[1]
  • Líneas celulares

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

  • Concentraciones

    10 μM

  • Tiempo de incubación

    ~100 hours

  • Método

    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.
Estudio en animales:

[1]
  • Modelos animales

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

  • Dosificaciones

    ~200 mg/kg daily

  • Administración

    p.o.

Referencias

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

Validación de productos por parte del cliente

<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.

Datos de [ , , 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).

Datos de [ , , 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.

Datos de [ , , Cancer Res, 2016, 76(22):6723-6734 ]

Sellecks LEE011 (Ribociclib) Ha sido citado por 116 Publicaciones

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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