Article
Oncology
Peibin Yue, Yinsong Zhu, Christine Brotherton-Pleiss, Wenzhen Fu, Nagendra Verma, Jasmine Chen, Kayo Nakamura, Weiliang Chen, Yue Chen, Felix Alonso-Valenteen, Simoun Mikhael, Lali Medina-Kauwe, Kathleen M. Kershaw, Maria Celeridad, Songqin Pan, Allison S. Limpert, Douglas J. Sheffler, Stephen L. Shiao, Marcus A. Tius, Francisco Lopez-Tapia, James Turkson
Summary: In this study, potent azetidine-based, selective, irreversible Stat3 inhibitors were identified that inhibit the growth of triple-negative breast cancer. These compounds amplify the Stat3-inhibitory activity and selectively bind to Stat3, leading to the inhibition of constitutive and ligand-induced Stat3 signaling. The inhibitors showed no effect on other proteins or cells without aberrantly-active Stat3.
Article
Chemistry, Medicinal
Lin Deng, Jianshan Mo, Yi Zhang, Keren Peng, Huaxuan Li, Shumin Ouyang, Zongbo Feng, Wei Fang, Jianwei Wei, Deqin Rong, Xiaolei Zhang, Yuanxiang Wang
Summary: Research has shown that targeting the STAT3-SH2 domain with a boronic acid group has the potential to be a new strategy for treating various human diseases. By replacing the carboxylic acid with a boronic acid, a highly potent inhibitor with stronger anticancer effects has been identified.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Anwar Zaiter, Zahraa F. Audi, Fatima Shawraba, Zahraa Saker, Hisham F. Bahmad, Rami H. Nabha, Hayat Harati, Sanaa M. Nabha
Summary: Medulloblastoma is the most common malignant brain tumor of childhood, with improved overall survival rate but still lacking efficient and reliable therapeutic approaches. Understanding the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis is crucial for the development of effective therapies.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Oncology
Huang Chen, Wenbo Zhou, Aiwu Bian, Qiansen Zhang, Ying Miao, Xuan Yin, Jiangnan Ye, Shifen Xu, Chaowen Ti, Zhenliang Sun, Jianghua Zheng, Yihua Chen, Mingyao Liu, Zhengfang Yi
Summary: This study identifies a novel drug called WB436B as a selective STAT3 inhibitor for the treatment of pancreatic cancer. WB436B effectively inhibits tumor growth and metastasis, providing hope for the treatment of pancreatic cancer.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Marta Gargantilla, Leentje Persoons, Tereza Kauerova, Natalia del Rio, Dirk Daelemans, Eva-Maria Priego, Peter Kollar, Maria-Jesus Perez-Perez
Summary: This study identified new salicylanilide compounds with antiproliferative activity against cancer cells by inhibiting tubulin polymerization and STAT3 phosphorylation, without toxicity towards normal cells.
Article
Chemistry, Medicinal
Peng He, Aiwu Bian, Ying Miao, Wangrui Jin, Huang Chen, Jia He, Liting Li, Yue Sun, Jiangnan Ye, Zhengfang Yi, Wenbo Zhou, Yihua Chen
Summary: This study reports the discovery of a series of novel STAT3 dual phosphorylation inhibitors with an indole-containing tetra-aromatic heterocycle scaffold. The optimal compound 4c showed desirable ADME properties and highly potent antitumor activities in vitro and in vivo. It has the potential to be a useful treatment option for pancreatic cancer as a STAT3 dual phosphorylation inhibitor.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Qi Huang, Jing Li, Mengqing Ma, Minling Lv, Rui Hu, Jialing Sun, Xin Zhong, Xinfeng Sun, Wenxing Feng, Wenfeng Ma, Wei Zhang, Bolin Zhan, Zhiyi Han, Xiaozhou Zhou
Summary: Polyphyllin VI, a natural herbal compound, was identified as a potential therapeutic drug for hepatocellular carcinoma (HCC). It inhibits the proliferation, invasion, and metastasis of HCC cells by inducing ferroptosis through the inhibition of the STAT3/GPX4 axis. These findings suggest that polyphyllin VI may have potential for the prevention and treatment of HCC.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ren Kong, Uddalak Bharadwaj, T. Kris Eckols, Mikhail Kolosov, Haoyi Wu, Francisco J. Santa Cruz-Pavlovich, Alison Shaw, Oluwatomilona I. Ifelayo, Hong Zhao, Moses M. Kasembeli, Stephen T. C. Wong, David J. Tweardy
Summary: Efforts to develop STAT3 inhibitors have mainly focused on its SH2 domain, with short phosphotyrosylated peptides and peptidomimetics showing high binding affinity but facing limitations in stability and bioavailability, leading to interest in small-molecule inhibitors. Through molecular dynamics simulations and structure-based virtual ligand screening, two potent, neutral, low-molecular weight STAT3-inhibitors with favorable drug-like properties were identified as promising candidates for anti-STAT3 drug development.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Oncology
Ranzhiqiang Yang, Yinghui Song, Kashif Shakoor, Weimin Yi, Chuang Peng, Sulai Liu
Summary: Intrahepatic cholangiocarcinoma (ICC) is a primary malignant liver tumor with a poor prognosis, characterized by neoplastic transformation of intrahepatic biliary epithelial cells. Signal transducer and activator of transcription 3 (STAT3) is an important oncogene that may serve as a target for ICC treatment. Further research is needed to improve understanding of STAT3 and its role in ICC development.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Immunology
Kosuke Miyauchi, Sewon Ki, Masao Ukai, Yoshie Suzuki, Kentaro Inoue, Wataru Suda, Takeshi Matsui, Yoshihiro Ito, Kenya Honda, Haruhiko Koseki, Osamu Ohara, Reiko J. Tanaka, Mariko Okada-Hatakeyama, Masato Kubo
Summary: The study suggests that STAT3 signaling in keratinocytes is essential for maintaining skin homeostasis by negatively regulating the expression of hair follicle-specific keratin genes. Expression patterns associated with dermatitis onset were observed under specific conditions, indicating the involvement of Toll-like receptor-mediated inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Jiangnan Ye, Huang Chen, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
Summary: This study describes the design, synthesis, and structure-activity relationship studies of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors. The best compound 3h (HP590) was discovered with high inhibitory activity against p-Tyr(705) and p-Ser(727), resulting in the growth inhibition of gastric cancer both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ri-Zhen Huang, Qiao-Ling Liang, Xiao-Teng Jing, Ke Wang, Hui-Yong Zhang, Heng-Shan Wang, Xian-Li Ma, Jian-Hua Wei, Ye Zhang
Summary: In this study, three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives were synthesized and identified as dual inhibitors of IDO1 and STAT3. Compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity, and further studies confirmed its direct interactions with IDO1 and STAT3 proteins. Compound NK3 showed potent antitumor activity and effectively suppressed nuclear translocation of STAT3 in vitro and exhibited potent antitumor activity with low toxicity in vivo. These findings suggest that dual inhibitors of IDO1 and STAT3 could be promising drug candidates for cancer therapy.
Review
Cell Biology
Yun Liu, Shijie Liao, Samuel Bennett, Haijun Tang, Dezhi Song, David Wood, Xinli Zhan, Jiake Xu
Summary: STAT3, a key protein involved in cell growth, differentiation, and survival, is overexpressed in osteosarcoma and various cancers. Its constitutive activation leads to upregulation of oncogenes, affecting processes such as transformation, proliferation, and metastasis.
CELL PROLIFERATION
(2021)
Article
Biochemistry & Molecular Biology
Feng Zhou, Fanyun Zhu, Tianru Zhu, Zhucheng Zhao, Luyao Li, Shichong Lin, Haiyang Zhao, Lehe Yang, Chengguang Zhao, Liangxing Wang, Jifa Li, Xiaoying Huang
Summary: AT7519, a CDK inhibitor, exhibits great anti-tumor effects in lung cancer by blocking IL-6/STAT3 pathway and inhibiting cell proliferation and inducing apoptosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Cardiac & Cardiovascular Systems
Lan Wu, Zhizheng Li, Yanfei Li
Summary: STAT3, as a transcription factor and signaling molecule, plays an important role in cardiac disease and protection. It regulates the expression of genes involved in oxidation, apoptosis, inflammation, and fibrosis. Additionally, it is also targeted and regulated by miRNAs, which further modulate the mRNA expression profiles in cardiomyocytes and impact cardiac disease and protection.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
