WP1066

WP1066 is a cell-permeable inhibitor of STAT3 that directs dephosphorylation and nuclear export of constitutively phosphorylated STAT3 in U87-MG and U373-MG malignant glioma cells when given at a concentration of 10 µM.¹ It also induces apoptosis in U87-MG (IC₅₀ = 5.6 µM) and U373-MG (IC₅₀ = 3.7 µM) cells.¹ WP1066 is orally bioavailable, crosses the blood-brain barrier, and demonstrates in vivo activity, including immune activation as indicated by the up-regulation of CD80 and CD86 and the induction of proliferation of effector T cells.^2,3 In addition to inducing apoptosis in cancer cells, WP1066 suppresses vascular smooth muscle cell proliferation after vascular injury in mice and prevents seizures following brain injury in rats.^4,5

WARNING This product is not for human or veterinary use.

1. Iwamura, A., Szymanski, S., Iwado, E., et al. A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene 26(17), 2435-2444 (2007).

2. Hussain, S.F., Kong, L.Y., Jordan, J., et al. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 67(20), 9630-9636 (2007).

3. Ferrajoli, A., Faderl, S., Van, Q., et al. WP1066 disrupts janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res. 67(23), 11291-11299 (2007).

4. Daniel, J.M., Dutzmann, J., Bielenberg, W., et al. Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation. Basic Res. Cardiol. 107(3), 261 (2012).

5. Grabenstatter, H.L., Cruz Del Angel, Y., Carlsen, J., et al. The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy. Neurobiol. Dis. 62, 73-85 (2013).