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WP1066

In stock
Catalog No.
A4140
JAK2/STAT3 inhibitor,cell-permeable
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$77.00
In stock
Evaluation Sample
$28.00
In stock
10mg
$70.00
In stock
25mg
$170.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

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Background

WP1066, an analogue of AG490, is a novel and potent inhibitor of janus kinase 2 (JAK2), which inhibits the phosphorylation of JAK2 and degrades JAK2 protein consequently blocking JAK2’s downstream signal transducer and activator of transcription (transcription-3 and transcription-5) as well as phosphoinositide-3-kinase pathways in a dose- and time-dependent manner. Results of preliminary studies suggest that WP1066 inhibits the growth of xenograft tumors generated from Caki-1 renal carcinoma cells (RCC) suppressing tumor angiogenesis and exhibits antiproliferative activity in AML colony-forming cells from newly diagnosed AML patients as well as in AML cell lines OCIM2 and K562, which potentiates it to treat RCC, acute myeloid leukemia (AML) and other hematologic maglignancies.

Reference

Srdan Verstovsek, Taghi Manshouri, Alfonso Quintas-Cardama, David Harris, Jorge Cortes, Francis J. Giles, Hagop Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res 2008; 14: 788-796

Alessandra Ferrajoli, Stefan Faderl, Quin Van, Patricia Koch, David Harris, Zhiming Liu, Inbal Hazan-Halevy, Yongtao Wang, Hagop M. Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066 disrupts janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res 2007; 67: 11291-11299

A Horiguchi, T Asano, K Kuroda, A Sato, J Asakuma, K Ito, M Hayakawa, M Sumitomo and T Asano.  STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. British Journal of Cancer 2010; 102: 1592-1599

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt356.22
Cas No.857064-38-1
FormulaC17H14BrN3O
Solubility≥17.8 mg/mL in DMSO, ≥24.6 mg/mL in EtOH with ultrasonic and warming, <2.54 mg/mL in H2O
Chemical Name(E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]prop-2-enamide
SDFDownload SDF
Canonical SMILESCC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

HEL cells carrying the mutant JAK2 V617F isoform

Preparation method

The solubility of this compound in DMSO is > 17.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0 ~ 6 μM; 72 hrs

Applications

In HEL cells carrying the mutant JAK2 V617F isoform, WP1066 markedly inhibited cell growth in a dose-dependent manner, with the IC20, IC50 and IC80 values of 0.8, 2.3 and 3.8 μM, respectively. At the concentrations of 0.5, 1.0, 2.0, 3.0 and 4.0 μM, WP1066 inhibited phosphorylation of JAK2, STAT3, STAT5 as well as ERK1/2, without affecting phosphorylation of JAK1 and JAK3.

Animal experiment [2]:

Animal models

Nude mice bearing Caki-1 cells

Dosage form

40 mg/kg; p.o.; q.d., 5 days on and 2 days off for 19 days

Applications

In nude mice bearing Caki-1 cells, WP1066 significantly inhibited tumor growth. The immunohistochemical analysis results of Caki-1 xenograft tumors showed that there was little p-STAT3 immunostaining in the WP1066 treatment group which had similar total STAT3 immunostaining as the vehicle group. The results suggested that WP1066 inhibited STAT3 phosphorylation without altering STAT3 expression.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Srdan Verstovsek, Taghi Manshouri, Alfonso Quintas-Cardama, David Harris, Jorge Cortes, Francis J. Giles, Hagop Kantarjian, Waldemar Priebe, and Zeev Estrov. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res 2008; 14: 788-796.

[2]. A Horiguchi, T Asano, K Kuroda, A Sato, J Asakuma, K Ito, M Hayakawa, M Sumitomo and T Asano. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. British Journal of Cancer 2010; 102: 1592-1599.

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.
Targets JAK2 STAT3        
IC50 2.3 μM 2.43 μM        

Quality Control

Chemical structure

WP1066

Related Biological Data

WP1066

Related Biological Data

WP1066