Review
Cell Biology
Jianbiao Zhou, Wee-Joo Chng
Summary: This article summarizes the role of STAT3 in multiple myeloma (MM), including its involvement in cell survival and proliferation, regulation of the tumor microenvironment, and induction of immunosuppression. The article also provides updates on different strategies for targeting STAT3 in MM, with a focus on JAK inhibitors currently undergoing clinical trials. Finally, the challenges and future directions of understanding STAT3 signaling and developing STAT3 inhibitors in MM are discussed.
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
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)
Article
Chemistry, Medicinal
Zhen Yu, Shixin Chan, Xu Wang, Ming Wang, Rui Sun, Zhenglin Wang, Xiaomin Zuo, Jiajie Chen, Huabing Zhang, Wei Chen
Summary: The combined therapy of 5-fluorouracil (5-FU) and rutaecarpine (RUT) showed significant inhibition of proliferation, migration, and anti-apoptotic ability of colorectal cancer (CRC) cells, both in vivo and in vitro. It was found that the therapy reduced the phosphorylation of STAT3 and influenced the STAT3 signaling pathway, leading to downregulation of c-Myc, CDK4, and Bcl-2 expression while enhancing cleaved caspase-3 expression.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Chemistry, Medicinal
Ko-Hua Yu, Chin-Chuan Hung, Tian-Shung Wu, Chin-Fu Chen, I-Ting Wu, Ping-Chung Kuo, Sio-Hong Lam, Hsin-Yi Hung
Summary: Research has shown that zhankuic acid methyl ester derivatives have better chemoreversal activity in multidrug-resistant cancer cells, with compound 12 exhibiting the highest reversal fold. Compounds 8, 12, and 26 were found to influence the activation of STAT3, contributing to their chemoreversal effects. These findings suggest a new potential combined therapy with paclitaxel for treating multidrug-resistant cancers.
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
Marine & Freshwater Biology
Rui Li, Yue Zhou, Xinxin Zhang, Lujia Yang, Jieyu Liu, Samantha M. Wightman, Ling Lv, Zhiqing Liu, Chang-Yun Wang, Chenyang Zhao
Summary: Through screening of marine natural products, a compound called Pretrichodermamide B was identified as a novel inhibitor of the JAK/STAT3 signaling pathway. It directly binds to STAT3, preventing phosphorylation and inhibiting the pathway. It also suppresses cancer cell growth and promotes apoptosis.
MARINE LIFE SCIENCE & TECHNOLOGY
(2023)
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)
Review
Pharmacology & Pharmacy
Matteo Santoni, Francesca Miccini, Alessia Cimadamore, Francesco Piva, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli
Summary: Researchers provided an overview of STAT3 inhibitors and examined the latest research results in cancer patients. They discussed recent publications since 2015 and ongoing clinical trials on anti-STAT3 agents in cancer patients. Future challenges include developing non-peptide small-molecule inhibitors of STAT3 and enhancing understanding of STAT3's role in modulating immune response.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
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)
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)
Article
Neurosciences
Xiaowei Qian, Ge Lin, Junpei Wang, Siming Zhang, Jingyi Ma, Bin Yu, Ronghua Wu, Mei Liu
Summary: The study reveals that circRNA_01477 promotes spinal astrocyte proliferation and migration after injury, and also contributes to axon growth in neurons by regulating the miRNA-3075/FosB/Stat3 axis.
EXPERIMENTAL NEUROLOGY
(2022)
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
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)
Article
Chemistry, Medicinal
Giulia Cazzaniga, Matteo Mori, Fiorella Meneghetti, Laurent R. Chiarelli, Giovanni Stelitano, Isabella Caligiuri, Flavio Rizzolio, Samuele Ciceri, Giulio Poli, Diana Staver, Gabriella Ortore, Tiziano Tuccinardi, Stefania Villa
Summary: A new compound with significant enzymatic activity against protein tyrosine phosphatase B, which interferes with host immune responses, has been discovered as a potential treatment for tuberculosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Matteo Mori, Giulia Cazzaniga, Fiorella Meneghetti, Stefania Villa, Arianna Gelain
Summary: This article provides an overview of interesting modulators of SIRT5, aiming to contribute to further developments in this field.
Article
Chemistry, Medicinal
Matteo Mori, Giovanni Stelitano, Anna Griego, Laurent R. Chiarelli, Giulia Cazzaniga, Arianna Gelain, Elena Pini, Marina Camera, Paola Canzano, Andrea Fumagalli, Edoardo Scarpa, Chiara Cordiglieri, Loris Rizzello, Stefania Villa, Fiorella Meneghetti
Summary: Tuberculosis is one of the most dangerous infectious diseases worldwide, and new therapeutic options are urgently needed. In this study, a series of analogues of the MbtI inhibitor were synthesized, and the most effective compound against TB was identified. Furthermore, a fluorescence-based screening test was established to accelerate the discovery of new anti-TB drugs.
Article
Chemistry, Physical
Alakbar Huseynzada, Matteo Mori, Fiorella Meneghetti, Aygun Israyilova, Gamze Tuzun, Koray Sayin, Laurent R. Chiarelli, Ceylan Mutlu, Mustafa Demiralp, Ulviyya Hasanova, Vagif Abbasov
Summary: The synthesis of a novel biologically active 3,4-dihydropyrimidin-2(1H)-thione derivative was reported, and the structure of the synthesized compound was investigated. The antibacterial effect of the compound was evaluated, and computational studies were performed to analyze its properties.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Organic
Alessio M. Caramiello, Maria Cristina Bellucci, Gaetano Cristina, Carlo Castellano, Fiorella Meneghetti, Matteo Mori, Francesco Secundo, Fiorenza Viani, Alessandro Sacchetti, Alessandro Volonterio
Summary: This study presents the synthesis of a collection of enantiomerically pure, systematically substituted hydantoins as structural privileged universal mimetic scaffolds. The synthesis relies on a selective condensation/cyclization process between isocyanates and aspartic acid diesters, followed by hydrolysis/coupling reactions with amines. Conformational studies showed that the hydantoin-based peptidomimetics are capable of projecting their substituents in positions superimposable to common protein secondary structures.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Editorial Material
Chemistry, Medicinal
Fiorella Meneghetti
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Crystallography
Alakbar Huseynzada, Matteo Mori, Fiorella Meneghetti, Aygun Israyilova, Elif Guney, Koray Sayin, Laurent R. Chiarelli, Mustafa Demiralp, Ulviyya Hasanova, Vagif Abbasov
Summary: In this study, methyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate 2 was prepared by the regioselective oxidative dehydrogenation of dihydropyrimidine derivative 1 in the presence of cerium ammonium nitrate. The tautomeric form of compound 2 was determined through single-crystal X-ray diffraction (SC-XRD). Non-covalent interactions and their impact on the crystal structure were analyzed using Hirshfeld surface and enrichment ratio analyses. Furthermore, the antimycotic activity of compounds 1 and 2 against Candida albicans, Aspergillus flavus, and Aspergillus niger was investigated and compared to fluconazole. Computational investigations provided insights into the better activity of compound 2 compared to its synthetic precursor.
Article
Pharmacology & Pharmacy
Matteo Mori, Giovanni Stelitano, Giulia Cazzaniga, Arianna Gelain, Andrea Tresoldi, Mario Cocorullo, Martina Roversi, Laurent R. R. Chiarelli, Martina Tomaiuolo, Pietro Delre, Giuseppe F. F. Mangiatordi, Anna Griego, Loris Rizzello, Alberto Cassetta, Sonia Covaceuszach, Stefania Villa, Fiorella Meneghetti
Summary: Targeting specific pathogenic mechanisms, including iron acquisition, shows potential for the development of new drugs against M. abscessus. In this study, the Salicylate Synthase (SaS) enzyme of Mab was investigated as a target for inhibitors of siderophore production. Compound 1 was identified as a lead inhibitor, exhibiting strong activity against Mab-SaS. Computational studies revealed key interactions between compound 1 and the enzyme, suggesting the potential for rational design of more potent derivatives.
Article
Chemistry, Organic
Matteo Mori, Andrea Tresoldi, Giulia Cazzaniga, Fiorella Meneghetti, Stefania Villa
Summary: This study presents the crystal structure analysis of a new class of antimycobacterial agents, providing important data support for further research.
Article
Chemistry, Organic
Matteo Mori, Andrea Tresoldi, Stefania Villa, Giulia Cazzaniga, Marco Bellinzoni, Fiorella Meneghetti
Summary: This article describes a new class of antitubercular agents, 5-phenyl-furan-2-carboxylic acids, and provides analysis methods and results for the compound.
Review
Biochemistry & Molecular Biology
Giovanni Stelitano, Mario Cocorullo, Matteo Mori, Stefania Villa, Fiorella Meneghetti, Laurent Roberto Chiarelli
Summary: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections is a crucial challenge in the scientific community. This review discusses innovative strategies to hinder iron acquisition in bacteria, including interesting targets and chemical entities that interfere with their function. The mechanism of action, pharmacodynamics, pharmacokinetics, and toxicological properties of each drug candidate are also reviewed. Comprehensive knowledge in this area may lead to the discovery of newer antibiotics to combat antimicrobial resistance effectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Samuele Ciceri, Diego Colombo, Enrico M. A. Fassi, Patrizia Ferraboschi, Giovanni Grazioso, Paride Grisenti, Marco Iannone, Carlo Castellano, Fiorella Meneghetti
Summary: Elagolix sodium salt is the first orally active non-peptide gonadotropin-releasing hormone receptor antagonist for the treatment of hormone dependent diseases. A detailed NMR investigation was conducted to analyze the drug and its synthetic intermediates, allowing for the complete assignment of the NMR signals and determination of the stereochemical profile of the atropisomers. These results contribute to the understanding of atropisomerism in drug discovery and can be applied in the design of safer and more effective analogs.
Article
Pharmacology & Pharmacy
Alessandro Ratti, Enrico M. A. Fassi, Fabio Forlani, Matteo Mori, Federica Villa, Francesca Cappitelli, Jacopo Sgrignani, Gabriella Roda, Andrea Cavalli, Stefania Villa, Giovanni Grazioso
Summary: Bacterial biofilm is a major cause of persistent infection and antibiotic resistance. This study investigates the antibiofilm properties and mode of action of ellagic acid (EA), a natural polyphenol. The researchers propose that EA disrupts the bacterial redox homeostasis mediated by the NADH:quinone oxidoreductase enzyme WrbA, leading to its antibiofilm activity. These findings provide new insights into the potential use of EA for treating biofilm-related infections.
Article
Biochemistry & Molecular Biology
Alessandro Ratti, Enrico M. A. Fassi, Fabio Forlani, Maurizio Zangrossi, Matteo Mori, Francesca Cappitelli, Gabriella Roda, Stefania Villa, Federica Villa, Giovanni Grazioso
Summary: This study used a computational model to screen natural compounds and identified purpurogallin and NZ034 as potential antibiofilm compounds at a non-lethal concentration of 0.5μM.
