Home JAK/STAT JAK inhibitor - STAT inhibitor - Apoptosis related activator WP1066 For research use only.

WP1066

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. WP1066 induces apoptosis. Phase 1.

WP1066 Chemical Structure

WP1066 Chemical Structure

CAS No. 857064-38-1

Purity & Quality Control

WP1066 Related Products

Signaling Pathway

JAK Signaling Pathways

JAK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MM1 cells Function assay 24-72 h Antitumor activity against human MM1 cells after 24 to 72 hrs by MTT assay, ic50=1.2 μM 22036213
human U266 cells Function assay 24-72 h Antitumor activity against human U266 cells after 24 to 72 hrs by MTT assay, IC50=1.5 μM 22036213
human OCI-My4 cells Function assay 24-72 h Antitumor activity against human OCI-My4 cells after 24 to 72 hrs by MTT assay, IC50=1.8 μM 22036213
human 30M cells Cytotoxic assay 8 days Cytotoxicity against human 30M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=1.8 μM 24900612
human 73M cells Cytotoxic assay 8 days Cytotoxicity against human 73M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=2.1 μM 24900612
human U373MG cells Function assay 24-72 h Antitumor activity against human U373MG cells after 24 to 72 hrs by MTT assay, IC50=3.7 μM 22036213
human U87MG cells Function assay 24-72 h Antitumor activity against human U87MG cells after 24 to 72 hrs by MTT assay, IC50=5.6 μM 22036213
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Biological Activity

Description WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. WP1066 induces apoptosis. Phase 1.
Features Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.
Targets
JAK2 [1]
(HEL cells)		 STAT3 [2]
(HEL cells)
2.3 μM 2.43 μM
In vitro
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. WP1066 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. [1] WP1066 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. WP1066 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. WP1066 at concentrations of 2 μM inhibits OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. WP1066 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. [3] WP1066 at concentrations of 5 μM prevents the phosphorylation of STAT3, and at concentrations of 2.5μM WP1066 significantly inhibits cell survival and proliferation in Caki-1 and 786-O renal cancer cells. WP1066 at concentrations of 5 μM suppresses HIF1α and HIF2α expression and VEGF production in Caki-1 and 786-O renal cancer cells. [4]
Cell Research Cell lines HEL cells carrying the JAK2 V617F mutant isoform, HL60, K562, Raji, PEER, CMK, TM and RHN cells
Concentrations 0 - 6 μM
Incubation Time 72 hours
Method 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 WP1066 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-STAT3 / STAT3 / p-ERK / ERK 20461084
Cell viability Cell viability 28496056
Immunofluorescence N-cadherin / E-cadherin / Vimentin / β-catenin 26690371
In Vivo
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. [4]
Animal Research Animal Models Caki-1 xenograft mice
Dosages 40 mg/kg
Administration Orally administrated
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04334863 Completed
Brain Tumor|Medulloblastoma|Brain Metastases
Emory University|CURE Childhood Cancer Inc.|Peach Bowl LegACy Fund
 May 4 2020 Phase 1

Chemical Information & Solubility

Molecular Weight 356.22 Formula

C17H14BrN3O
CAS No. 857064-38-1 SDF Download WP1066 SDF
Smiles CC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 71 mg/mL ( (199.31 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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