1334493-07-0Relevant articles and documents
Design, synthesis, and in?vitro evaluation of BP-1-102 analogs with modified hydrophobic fragments for STAT3 inhibition
Oleksak, Patrik,Psotka, Miroslav,Vancurova, Marketa,Sapega, Olena,Bieblova, Jana,Reinis, Milan,Rysanek, David,Mikyskova, Romana,Chalupova, Katarina,Malinak, David,Svobodova, Jana,Andrys, Rudolf,Rehulkova, Helena,Skopek, Vojtech,Ngoc Lam, Pham,Bartek, Jiri,Hodny, Zdenek,Musilek, Kamil
, p. 410 - 424 (2021/02/05)
Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel co
Potent targeting of the STAT3 protein in brain cancer stem cells: A promising route for treating glioblastoma
Haftchenary, Sina,Luchman, H. Artee,Jouk, Andriana O.,Veloso, Anthony J.,Page, Brent D. G.,Cheng, Xin Ran,Dawson, Sean S.,Grinshtein, Natalie,Shahani, Vijay M.,Kerman, Kagan,Kaplan, David R.,Griffin, Carly,Aman, Ahmed M.,Al-Awar, Rima,Weiss, Samuel,Gunning, Patrick T.
, p. 1102 - 1107 (2013/12/04)
The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (KD = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.
Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain
Page, Brent D.G.,Fletcher, Steven,Yue, Peibin,Li, Zhihua,Zhang, Xiaolei,Sharmeen, Sumaiya,Datti, Alessandro,Wrana, Jeffrey L.,Trudel, Suzanne,Schimmer, Aaron D.,Turkson, James,Gunning, Patrick T.
, p. 5605 - 5609 (2011/10/09)
Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promis