Article
Oncology
Xiyuan Lu, Lina Han, Jonathan Busquets, Meghan Collins, Alessia Lodi, Joseph R. Marszalek, Marina Konopleva, Stefano Tiziani
Summary: A novel synergistic drug combination of the oxidative phosphorylation inhibitor IACS-010759 and the FMS-like tyrosine kinase 3 (FLT3) inhibitor AC220 was found to inhibit cell growth in AML by disrupting cell metabolism.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daria Monogiou Belik, Riccardo Bernasconi, Lifen Xu, Giacomo Della Verde, Vera Lorenz, Vivienne Gruterich, Melania Balzarolo, Michika Mochizuki, Otmar Pfister, Gabriela M. Kuster
Summary: This study aimed to test whether Flt3-targeting TKI treatment aggravates cardiac injury after myocardial infarction (MI). The results showed that quizartinib did not alter cardiac dimensions or function in healthy mice, but significantly enhanced ventricular dilatation and apoptotic cell death in MI mice. In vitro studies further confirmed that quizartinib increased cell death and apoptosis, potentially through a p38-dependent mechanism.
Review
Oncology
Jayastu Senapati, Tapan Mahendra Kadia
Summary: Treatment options in acute myeloid leukemia (AML) have significantly improved over the last decade, with better understanding of disease biology and availability of targeted therapies. The use of FLT3 inhibitors (FLT3i) in FLT3-mutated (FLT3(mut)) AML is an important development, but the clinical decisions and choice of FLT3i are still evolving.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu
Summary: This study investigates the mechanisms of TFIID and Mediator proteins in regulating transcription initiation and RNA polymerase activity, revealing their interactions and mutual regulation through structural analysis, as well as the phosphorylation process of Pol II CTD by CDK7.
Article
Biology
Fangmin Huang, Jiankun Liang, Yingying Lin, Yushi Chen, Fen Hu, Jianting Feng, Qiang Zeng, Zeteng Han, Qiaofa Lin, Yan Li, Jingyi Li, Lanqin Wu, Lisheng Li
Summary: A study discovered multiple compounds that inhibit TNF-induced necroptosis by screening a compound library. These compounds were classified into different groups based on their mechanisms of action. Further investigation identified Ibrutinib as an inhibitor of RIPK3 and Quizartinib as a protector against TNF-induced systemic inflammatory response syndrome by inhibiting the activation of RIPK1. The findings suggest new potential approaches for treating necroptosis-related diseases.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Zhijie Wang, Jiongheng Cai, Jiwei Ren, Yun Chen, Yingli Wu, Jie Cheng, Kun Jia, Fei Huang, Zitian Cheng, Tiancheng Sheng, Shiyu Song, Hao Heng, Yifan Zhu, Weifang Tang, Hongmei Li, Tao Lu, Yadong Chen, Shuai Lu
Summary: Secondary mutations of FLT3 pose a significant clinical challenge in FLT3 inhibitor resistance. A series of novel compounds, with compound 67 showing potent inhibitory activity against FLT3-ITD-positive AML cells and cells with various secondary mutations, may serve as a promising drug candidate for the treatment of FLT3-ITD-positive AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Kailong Jiang, Xuemei Li, Chang Wang, Xiaobei Hu, Peipei Wang, Lexian Tong, Yutong Tu, Beijing Chen, Tingting Jin, Tao Wang, Hanlin Wang, Yubing Han, Renzhao Gui, Jianmin Yang, Tao Liu, Jia Li, Yubo Zhou
Summary: FLT3 inhibitors (FLT3i) are widely used for AML treatment, but adaptive and acquired resistance remains a challenge. This study found that CHK1 inhibitors can synergistically enhance the therapeutic effect of FLT3i in FLT3-mutated AML cells, overcoming adaptive resistance. Simultaneous targeting of FLT3 and CHK1 may overcome acquired and adaptive resistance.
Article
Hematology
Shuai-Shuai Ge, Qiao-Cheng Qiu, Hai-Ping Dai, Xiang-Dong Shen, Tian-Mei Wu, Jia-Hui Du, Chao-Ling Wan, Hong-Jie Shen, De-Pei Wu, Sheng-Li Xue, Song-Bai Liu
Summary: In this study, the spectrum of FLT3 mutations in haematological malignancies was investigated. Four types of non-canonical FLT3 mutations were identified, including non-canonical point mutations, deletion, frameshift, and ITD outside the JMD and TKD1 regions. The survival of patients with high-frequency FLT3-NCPM in AML was shown to be comparable to those with canonical TKD mutations. Additionally, certain deletion and ITD mutants showed higher kinase activity than wild-type FLT3, and all tested deletion mutations and ITD were sensitive to AC220 and sorafenib.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Microbiology
Zhiwei Kong, Xin Zhang, Feng Zhou, Liu Tang, Yitong Chen, Saijie Li, Xiaokang Zhang, Letian Kuai, Wenji Su, Weiren Cui, Jiaxi Cai, Yuli Wang, Jun Yang, You-Liang Peng, Dongli Wang, Junfeng Liu
Summary: Rice blast, caused by M. oryzae, is a devastating disease that affects cultivated rice. Chemical control and the discovery of novel fungicide targets are important for managing the disease. Mps1 is a fungal protein that plays a critical role in plant cell wall penetration during infection. A small-molecule inhibitor, A378-0, has been identified to target Mps1 and inhibit the growth of M. oryzae. This discovery suggests that Mps1 and its orthologs can be potential fungicide targets for developing broad-spectrum fungicides.
Article
Multidisciplinary Sciences
Hua Li, E. Sethe Burgie, Zachary T. K. Gannam, Huilin Li, Richard D. Vierstra
Summary: This study reports the cryo-electron microscopy structure of Arabidopsis PhyB in the Pr state, revealing a complex dimeric organization that is distinct from its prokaryotic relatives. The study also reveals connections between dimer assembly and Pfr stability, as well as asymmetry between the HKRDs and the platform. The unique structural dynamism creates a photostate-sensitive surface for conformation-dependent interactions between plant Phy photoreceptors and their signaling partners.
Article
Biochemistry & Molecular Biology
James L. Walshe, Rezwan Siddiquee, Karishma Patel, Sandro F. Ataide
Summary: Regulated transcription termination provides a means to control gene expression. ANTAR domains bind and stabilize RNA structures to prevent termination. Our study on EutV protein reveals the specific interaction between ANTAR domains and a single hexaloop RNA motif, which is essential for preventing termination. These findings have implications for discovering novel ANTAR domain RNA targets.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Masoumeh Divar, Najmeh Edraki, Tahereh Damghani, Fatemeh Moosavi, Maryam Mohabbati, Alireza Alipour, Somayeh Pirhadi, Luciano Saso, Soghra Khabnadideh, Omidreza Firuzi
Summary: Despite advances in therapeutic strategies, cancer remains a leading cause of death. This study synthesized a new series of spiro[indoline-3,2'-quinazoline]-2,4'(3'H)-dione derivatives and evaluated their potential as kinase inhibitors with anti-cancer effects. The most promising compounds exhibited anti-proliferative activity against various cancer cell lines and altered the distribution of cells in the cell cycle. FLT3 kinase was identified as the primary target of these compounds. Compound 5f showed potent inhibitory activity against wild-type FLT3 and its mutant, D835Y. Docking and simulation studies revealed the important interactions of compound 5f with FLT3. These findings suggest that these spiroindoline quinazolinedione compounds could be promising candidates for novel anticancer drugs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Lixin Zhou, Tianyu Wang, Kuojun Zhang, Xiangyu Zhang, Sheng Jiang
Summary: Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine protein kinase that negatively regulates T cells, B cells, and dendritic cells-mediated immune responses. It plays a role in cellular processes such as immune cell activation, differentiation, proliferation, adhesion, and apoptosis. HPK1 is associated with the occurrence and development of human malignant tumors, making it a promising target for cancer immunotherapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Seiji Fukuda, Nozomi Matsuda, Tsukimi Shoji, Chie Onishi, Tomohiro Hirade, Takeshi Taketani, Louis M. Pelus
Summary: CXCR4 has divergent effects on FLT3/ITD+ AML cells, with low concentrations of CXCL12 protecting against FLT3 inhibitor quizartinib and high concentrations promoting cell apoptosis. The expression of CXCR4 is correlated with the expression of RUNX1 and the phosphorylation status of FLT3.
Article
Multidisciplinary Sciences
R. Abdella, A. Talyzina, S. Chen, C. J. Inouye, R. Tjian, Y. He
Summary: Eukaryotic transcription requires the assembly of a multisubunit preinitiation complex (PIC) composed of RNA polymerase II (Pol II) and general transcription factors. The coactivator Mediator is recruited by transcription factors to facilitate assembly of the PIC and stimulate phosphorylation of Pol II C-terminal domain (CTD). Transcription factor binding sites in Mediator are primarily flexibly tethered to the tail module, while CDK7 is stabilized through multiple contacts with Mediator. Two binding sites for Pol II CTD exist, providing structural evidence for phosphorylation within the Mediator-bound PIC.
Review
Biochemistry & Molecular Biology
Erika Kovacs, Julie Anne Zorn, Yongjian Huang, Tiago Barros, John Kuriyan
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 84
(2015)
Article
Biochemistry & Molecular Biology
Patrick R. Visperas, Jonathan A. Winger, Timothy M. Horton, Neel H. Shah, Diane J. Aum, Alyssa Tao, Tiago Barros, Qingrong Yan, Christopher G. Wilson, Michelle R. Arkin, Arthur Weiss, John Kuriyan
BIOCHEMICAL JOURNAL
(2015)
Article
Biochemistry & Molecular Biology
Erika Kovacs, Rahul Das, Qi Wang, Timothy S. Collier, Aaron Cantor, Yongjian Huang, Kathryn Wong, Amar Mirza, Tiago Barros, Patricia Grob, Natalia Jura, Ron Bose, John Kuriyan
MOLECULAR AND CELLULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Margaret E. Brown, Tiago Barros, Michelle C. Y. Chang
ACS CHEMICAL BIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Qingrong Yan, Tiago Barros, Patrick R. Visperas, Sebastian Deindl, Theresa A. Kadlecek, Arthur Weiss, John Kuriyan
MOLECULAR AND CELLULAR BIOLOGY
(2013)
Article
Multidisciplinary Sciences
Stefan Bode, Claudia C. Quentmeier, Pen-Nan Liao, Nour Hafi, Tiago Barros, Laura Wilk, Florian Bittner, Peter J. Walla
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2009)
Review
Biochemistry & Molecular Biology
Nicholas F. Endres, Tiago Barros, Aaron J. Cantor, John Kuriyan
TRENDS IN BIOCHEMICAL SCIENCES
(2014)
Article
Biophysics
Tiago Barros, Joel Guenther, Brian Kelch, Jordan Anaya, Arjun Prabhakar, Mike O'Donnell, John Kuriyan, Meindert H. Lamers
BMC STRUCTURAL BIOLOGY
(2013)
Article
Biology
Jeffrey S. Iwig, Yvonne Vercoulen, Rahul Das, Tiago Barros, Andre Limnander, Yan Che, Jeffrey G. Pelton, David E. Wemmer, Jeroen P. Roose, John Kuriyan
Editorial Material
Multidisciplinary Sciences
Flaminio Squazzoni, Petra Ahrweiler, Tiago Barros, Federico Bianchi, Aliaksandr Birukou, Harry J. J. Blom, Giangiacomo Bravo, Stephen Cowley, Virginia Dignum, Pierpaolo Dondio, Francisco Grimaldo, Lynsey Haire, Jason Hoyt, Phil Hurst, Rachael Lammey, Catriona MacCallum, Ana Marusic, Bahar Mehmani, Hollydawn Murray, Duncan Nicholas, Giorgio Pedrazzi, Iratxe Puebla, Peter Rodgers, Tony Ross-Hellauer, Marco Seeber, Kalpana Shankar, Joris Van Rossum, Michael Willis
Review
Medicine, General & Internal
Anna Severin, Michaela Strinzel, Matthias Egger, Marc Domingo, Tiago Barros
Summary: The study analyzed the characteristics of scholars who reviewed for predatory or legitimate journals, finding that most scholars never reviewed for predatory journals and those who did were typically younger and had fewer publications and reviews. Regions with the highest shares of predatory reviews were sub-Saharan Africa, Middle East and North Africa, and South Asia. To combat predatory journals, it is important for universities, funders, and publishers to educate reviewers on quality and legitimacy in scholarly publishing.
Article
Biochemistry & Molecular Biology
Anna Severin, Michaela Strinzel, Matthias Egger, Tiago Barros, Alexander Sokolov, Julia Vilstrup Mouatt, Stefan Mueller
Summary: This study analyzed 10,000 peer review reports from 1,644 biomedical journals and found that peer review in higher impact factor journals tends to be more thorough in addressing study methods but gives relatively less emphasis to presentation and suggesting solutions. This indicates that the Journal Impact Factor is a poor predictor of the quality of peer review.
Article
Biology
Moitrayee Bhattacharyya, Margaret M. Stratton, Catherine C. Going, Ethan D. McSpadden, Yongjian Huang, Anna C. Susa, Anna Elleman, Yumeng Melody Cao, Nishant Pappireddi, Pawel Burkhardt, Christine L. Gee, Tiago Barros, Howard Schulman, Evan R. Williams, John Kurivan
Proceedings Paper
Chemistry, Physical
Sergiu Amarie, Laura Wilk, Tiago Barros, Werner Kuehlbrandt, Andreas Dreuw, Josef Wachtveitl
ULTRAFAST PHENOMENA XVI
(2009)