1241833-06-6Relevant articles and documents
Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors
Brotherton-Pleiss, Christine,Yue, Peibin,Zhu, Yinsong,Nakamura, Kayo,Chen, Weiliang,Fu, Wenzhen,Kubota, Casie,Chen, Jasmine,Alonso-Valenteen, Felix,Mikhael, Simoun,Medina-Kauwe, Lali,Tius, Marcus A.,Lopez-Tapia, Francisco,Turkson, James
supporting information, p. 695 - 710 (2021/01/14)
We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of (R)-azetidine-2-carboxamide analogues that have sub-micromolar potencies. 5a, 5o, and 8i have STAT3-inhibitory potencies (IC50) of 0.55, 0.38, and 0.34 μM, respectively, compared to potencies greater than 18 μM against STAT1 or STAT5 activity. Further modifications derived analogues, including 7e, 7f, 7g, and 9k, that addressed cell membrane permeability and other physicochemical issues. Isothermal titration calorimetry analysis confirmed high-affinity binding to STAT3, with KD of 880 nM (7g) and 960 nM (9k). 7g and 9k inhibited constitutive STAT3 phosphorylation and DNA-binding activity in human breast cancer, MDA-MB-231 or MDA-MB-468 cells. Furthermore, treatment of breast cancer cells with 7e, 7f, 7g, or 9k inhibited viable cells, with an EC50 of 0.9-1.9 μM, cell growth, and colony survival, and induced apoptosis while having relatively weaker effects on normal breast epithelial, MCF-10A or breast cancer, MCF-7 cells that do not harbor constitutively active STAT3.
Substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs as inhibitors of STAT protein
-
, (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
Linker Variation and Structure-Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors
Lopez-Tapia, Francisco,Brotherton-Pleiss, Christine,Yue, Peibin,Murakami, Heide,Costa Araujo, Ana Carolina,Reis Dos Santos, Bruna,Ichinotsubo, Erin,Rabkin, Anna,Shah, Raj,Lantz, Megan,Chen, Suzie,Tius, Marcus A.,Turkson, James
supporting information, p. 250 - 255 (2018/03/21)
The molecular determinants for the activities of the reported benzoic acid (SH4-54), salicylic acid (BP-1-102), and benzohydroxamic acid (SH5-07)-based STAT3 inhibitors were investigated to design optimized analogues. All three leads are based on an N-met
2-ARYLSULFONAMIDO-N-ARYLACETAMIDE DERIVATIZED STAT3 INHIBITORS
-
Paragraph 00550, (2018/08/20)
The present disclosure provides pharmaceutical compositions comprising 2-arylsulfonamido-N-arylacetamide derivatized Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use.
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.
, 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