1241833-16-8Relevant academic research and scientific papers
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
Substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs as inhibitors of STAT protein
-
Page/Page column 226-227; 229-230, (2019/02/14)
In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the com
Identification of bidentate salicylic acid inhibitors of PTP1B
Haftchenary, Sina,Jouk, Andriana O.,Aubry, Isabelle,Lewis, Andrew M.,Landry, Melissa,Ball, Daniel P.,Shouksmith, Andrew E.,Collins, Catherine V.,Tremblay, Michel L.,Gunning, Patrick T.
supporting information, p. 982 - 986 (2015/09/22)
PTP1B is a master regulator in the insulin and leptin metabolic pathways. Hyper-activated PTP1B results in insulin resistance and is viewed as a key factor in the onset of type II diabetes and obesity. Moreover, inhibition of PTP1B expression in cancer cells dramatically inhibits cell growth in vitro and in vivo. Herein, we report the computationally guided optimization of a salicylic acid-based PTP1B inhibitor 6, identifying new and more potent bidentate PTP1B inhibitors, such as 20h, which exhibited a > 4-fold improvement in activity. In CHO-IR cells, 20f, 20h, and 20j suppressed PTP1B activity and restored insulin receptor phosphorylation levels. Notably, 20f, which displayed a 5-fold selectivity for PTP1B over the closely related PTPσ protein, showed no inhibition of PTP-LAR, PRL2 A/S, MKPX, or papain. Finally, 20i and 20j displayed nanomolar inhibition of PTPσ, representing interesting lead compounds for further investigation.
Inhibiting aberrant signal transducer and activator of transcription protein activation with tetrapodal, small molecule Src homology 2 domain binders: Promising agents against multiple myeloma
Page, Brent D. G.,Croucher, Danielle C.,Li, Zhi Hua,Haftchenary, Sina,Jimenez-Zepeda, Victor H.,Atkinson, Jennifer,Spagnuolo, Paul A.,Wong, Yoong Lim,Colaguori, Robert,Lewis, Andrew M.,Schimmer, Aaron D.,Trudel, Suzanne,Gunning, Patrick T.
supporting information, p. 7190 - 7200 (2013/10/21)
The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3-4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity in vitro. These compounds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations.
NEW SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
-
Page/Page column 54; 66, (2014/01/07)
The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.
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.
Antagonism of the Stat3-Stat3 Protein Dimer with Salicylic Acid Based Small Molecules
Fletcher, Steven,Page, Brent D.G.,Zhang, Xialoei,Yue, Peibin,Li, Zhi Hua,Sharmeen, Sumaiya,Singh, Jagdeep,Zhao, Wei,Schimmer, Aaron D.,Trudel, Suzanne,Turkson, James,Gunning, Patrick T.
scheme or table, p. 1459 - 1470 (2012/07/01)
More than 50 new inhibitors of the oncogenic Stat3 protein were identified through a structure-activity relationship (SAR) study based on the previously identified inhibitor S3I-201 (IC50=86μM, Ki>300μM). A key structural feature of
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
