857064-38-1

Usage

Uses

Used in Cancer Therapy:
WP1066 is used as a targeted treatment for malignant glioma cells, specifically U87-MG and U373-MG, due to its ability to induce apoptosis and inhibit the activity of STAT3, a protein often implicated in the regulation of cell growth and apoptosis.
Used in Neuroprotection:
WP1066 is utilized for its neuroprotective properties, as it has been shown to prevent seizures following brain injury in rats, highlighting its potential use in the treatment of neurological conditions associated with brain trauma.
Used in Cardiovascular Health:
In the context of cardiovascular health, WP1066 is used to suppress the proliferation of vascular smooth muscle cells after vascular injury in mice, which may contribute to the prevention of restenosis and other vascular complications following interventions.
Used in Immunomodulation:
WP1066 is employed as an immunomodulatory agent, as it has demonstrated the capability to activate the immune system by up-regulating CD80 and CD86 and inducing the proliferation of effector T cells, which could be beneficial in the development of immunotherapies for various diseases.

References

1) Kong?et al.?(2005),?Discovery of WP1066, a novel Stat3/c-myc inhibitor with potent antitumor activity against human melanoma in vitro and in vivo;?Cancer Res.?65?1387 2) Iwamaru?et al.?(2007),?A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both invitro and in vivo;?Oncogene?26?2435 3) Ferraioli?et al.?(2007),?WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in acute Myelogenous Leukemia Cells;?Cancer Res.?67?11291 4) Kong,?et al.?(2008),?A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells;?Clin. Cancer Res.?14?5759 5) Kong,?et al.?(2009),?A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells;?Cancer Immunol. Immunother.?58?1023 6) Ma,?et al.?(2017),?Stat3 inhibitor abrogates the expression of PD-1 ligands on Lymphoma cell lines;?J. Clin. Exp. Hematop.?57?21

Upstream product

• 34160-40-2 6-bromo-2-pyridinecarbaldehyde 
• 1240041-69-3 C₁₁H₁₂N₂O 

Relevant academic research and scientific papers

Preclinical characterization of signal transducer and activator of transcription 3 small molecule inhibitors for primary and metastatic brain cancer therapy

Signal transducer and activator of transcription 3 (STAT3) has been implicated as a hub for multiple oncogenic pathways. The constitutive activation of STAT3 is present in several cancers, including gliomas (GBMs), and is associated with poor therapeutic responses. Phosphorylation of STAT3 triggers its dimerization and nuclear transport, where it promotes the transcription of genes that stimulate tumor growth. In light of this role, inhibitors of the STAT3 pathway are attractive therapeutic targets for cancer. To this end, we evaluated the STAT3-inhibitory activities of three compounds (CPA-7 [trichloronitritodiammineplatinum(IV)], WP1066 [(S,E)-3-(6-bromopyridin-2-yl)-2- cyano-N-(1-phenylethyl)acrylamide, C17H14BrN 3O], and ML116 [4-benzyl-1-{thieno[2,3-d]pyrimidin-4-yl}piperidine, C18H19N3S]) in cultured rodent and human glioma cells, including GBM cancer stem cells. Our results demonstrate a potent induction of growth arrest in GBM cells after drug treatment with a concomitant induction of cell death. Although these compounds were effective at inhibiting STAT3 phosphorylation, they also displayed variable dose-dependent inhibition of STAT1, STAT5, and nuclear factor κ light-chain enhancer of activated B cells. The therapeutic efficacy of these compounds was further evaluated in peripheral and intracranial mouse tumor models. Whereas CPA-7 elicited regression of peripheral tumors, both melanoma and GBM, its efficacy was not evident when the tumors were implanted within the brain. Our data suggest poor permeability of this compound to tumors located within the central nervous system. WP1066 and ML116 exhibited poor in vivo efficacy. In summary, CPA-7 constitutes a powerful anticancer agent in models of peripheral solid cancers. Our data strongly support further development of CPA- 7-derived compounds with increased permeability to enhance their efficacy in primary and metastatic brain tumors. Copyright

COMPOUNDS FOR TREATMENT OF CELL PROLIFERATIVE DISEASES

The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as kinase inhibitors, cause the downregulation of c-myc, and inhibit the growth and survival of cancerous cell lines.