WP1066 (Synonyms: STAT Inhibitor III)

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 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.