WP1066

N.º de catálogoS2796 Lote:S279602

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Datos técnicos

Fórmula

C17H14BrN3O
Peso molecular 356.22 Número CAS 857064-38-1
Solubilidad (25°C)* In vitro DMSO 71 mg/mL (199.31 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.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, póngase en contacto con nuestro equipo de ventas para pruebas personalizadas.

 4.000mg/ml (11.23mM) Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 WP1066 es un nuevo inhibidor de JAK2 y STAT3 con IC50 de 2,30 μM y 2,43 μM en células HEL; muestra actividad hacia JAK2, STAT3, STAT5 y ERK1/2, pero no hacia JAK1 y JAK3. WP1066 induce apoptosis. Fase 1.
Objetivos
JAK2
(HEL cells)		 STAT3
(HEL cells)
2.3 μM 2.43 μM
In vitro WP1066 markedly inhibits the growth of HEL cells carrying the JAK2 V617F mutant isoform in a dose-dependent manner with IC20, IC50 and IC80 of 0.8, 2.3 and 3.8 μM. This compound at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM inhibits the phosphorylation of JAK2, STAT3, STAT5, and ERK1/2 without affecting the phosphorylation of JAK1 and JAK3 in erythroid leukemia HEL cells that express the JAK2 V617F isoform. It at concentrations ranging from 0.5 to 3.0 μM inhibits the proliferation of AML colony-forming cells obtained from patients and that of the AML cell lines OCIM2 and K562 in a dose-dependent manner. This chemical at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM dose-dependently decreases JAK2 and pJAK2 protein levels as well as downstream phosphorylation levels of STAT3, STAT5, and AKT in OCIM2 and K562 cells. It at concentrations of 2 μM inhibits OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. This compound at concentrations of 1, 2, or 3 μM induces apoptosis in both OCIM2 and K562 cells in a dose-dependent fashion by activating procaspase-3 and cleaving PARP. It at concentrations of 5 μM prevents the phosphorylation of STAT3, and at concentrations of 2.5μM it significantly inhibits cell survival and proliferation in Caki-1 and 786-O renal cancer cells. This chemical at concentrations of 5 μM suppresses HIF1α and HIF2α expression and VEGF production in Caki-1 and 786-O renal cancer cells.
In vivo WP1066 orally administrated at dose of 40 mg/kg once daily for 19 days significantly inhibits the tumours growth in Caki-1 xenograft mice, with decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels.
Características Similar a su compuesto parental AG490, WP1066 inhibe la fosforilación de JAK2, pero a diferencia de AG490, WP1066 también degradó la proteína JAK2.

Protocolo (de referencia)

Ensayo celular:[1]
  • Líneas celulares

    HEL cells carrying the JAK2 V617F mutant isoform, HL60, K562, Raji, PEER, CMK, TM and RHN cells

  • Concentraciones

    0 - 6 μM

  • Tiempo de incubación

    72 hours

  • Método

    The 3, [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTT) assay is done using an MTT-based cell proliferation/cytotoxicity assay system. Briefly, fresh low-density peripheral blood cells and various cell lines at the logarithmic phase of their growth are washed twice in RPMI 1640 containing 10% FCS and counted in a hemocytometer. Cell viability is assessed by the trypan blue (0.1%) staining method. Equal numbers of viable cells (5 × 104 per well) are incubated in a total volume of 100 μL of RPMI 1640 supplemented with 10% FCS alone or with this compound at increasing concentrations; the incubations are continued for up to 72 h in 96-well flat-bottomed plates at 37 °C in a humidified 5% CO2 atmosphere. Experiments for each condition are done in triplicate. After incubation, 20 μL of CellTiter96 One Solution Reagent are added to each well. The plates are then incubated for an additional 60 min at 37 °C in a humidified 5% CO2 atmosphere. Immediately after incubation, absorbance is read using a 96-well plate reader at a wavelength of 490 nm.
Estudio en animales:[4]
  • Modelos animales

    Caki-1 xenograft mice

  • Dosificaciones

    40 mg/kg

  • Administración

    Orally administrated

Referencias

  • https://pubmed.ncbi.nlm.nih.gov/18245540/
  • https://pubmed.ncbi.nlm.nih.gov/21792892/
  • https://pubmed.ncbi.nlm.nih.gov/18056455/
  • https://pubmed.ncbi.nlm.nih.gov/20461084/

Validación de productos por parte del cliente

Effects of selective STAT3 inhibitors on adherent glioma CSCs. Cells were treated with WP1066 (50 uM for 2 h) or vehicle, and colocalization of STAT3 and p65 was determined by immunostaining.

Datos de [ J Biol Chem , 2013 , 288(36), 26167-76 ]

<div>proliferation of GBM6 monolayer and adherent CSC cultures was measured by MTT assay after treatment (72 h) with WP1066 or S3I-201 at the indicated concentrations. </div>

,

BrdU assay for the proliferation of WP1066- treated UM1 and Tca8113 cells (P<0.05).

Datos de [ , , Clin Cancer Res, 2018, 24(11):2665-2677 ]

(A) HRMECs were treated with IL-6 for 48 hours in the presence and the absence of WP1066. The protein expression and localization of ZO-1 was examined by immunofluorescence staining. Each tight junction protein was doubleimmunostained with anti-CD31 antibody for defining the cell boundaries. Nuclei were labeled with DAPI. Arrow heads indicate the intact tight junction protein at cell boundaries. Scale bars are equal to 50 μm. Right histograms: quantitative analysis of each tight junction protein expression by evaluating the fluorescence intensity using with ImageJ software. The results are fold increases versus control and plotted as the means ± SD (n = 5). * P < 0.05 between two values.

Datos de [ , , J Cell Physiol, 2017, 232(5):1123-1134 ]

Selleck's WP1066 Ha sido citado por 76 Publicaciones

NIBAN2 Stimulates Glioma Growth by Regulating the JAK2/STAT3/c-Myc Pathway [ Cancer Med, 2025, 14(18):e71239] PubMed: 40944417
Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression [ Nat Commun, 2024, 15(1):1987] PubMed: 38443336
IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion [ Cancer Cell Int, 2024, 24(1):60] PubMed: 38326861
RNF122 promotes glioblastoma growth via the JAK2/STAT3/c-Myc signaling Axis [ CNS Neurosci Ther, 2024, 30(9):e70017] PubMed: 39218810
Investigation of cuproptosis regulator-mediated modification patterns and SLC30A7 function in GBM [ Aging (Albany NY), 2024, 16(4):3554-3582] PubMed: 38393693
P. gingivalis Infection Upregulates PD-L1 Expression on Dendritic Cells, Suppresses CD8+ T-cell Responses, and Aggravates Oral Cancer [ Cancer Immunol Res, 2023, 11(3):290-305] PubMed: 36633576
Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2 [ Brain Pathol, 2023, 10.1111/bpa.13212] PubMed: 37721122
oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy [ Mol Ther Oncolytics, 2023, 29:30-41] PubMed: 37114074
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ Int Immunopharmacol, 2023, 118:109993] PubMed: 36931170
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ International Immunopharmacology, 2023, Volume 118] PubMed: None

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