Article
Medicine, General & Internal
Jeannig Berrou, Melanie Dupont, Hanane Djamai, Emilie Adiceam, Veronique Parietti, Anna Kaci, Emmanuelle Clappier, Jean-Michel Cayuela, Andre Baruchel, Fabrice Paublant, Renaud Prudent, Jacques Ghysdael, Claude Gardin, Herve Dombret, Thorsten Braun
Summary: This study demonstrates that LIMKi CEL_Amide has anti-leukemic effects in Ph+ ALL models when combined with BCR::ABL-targeting TKIs, showing promising synergy that warrants further investigation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Rajashri R. Naik, Ashok K. Shakya
Summary: Protein kinases transfer phosphate to proteins, modifying their structure. The human genome contains approximately 538 kinases, which play a crucial role in various cellular processes. Dysregulation of kinases is associated with the development of diseases, particularly cancer. Understanding the mechanisms and roles of kinases has led to the development of kinase inhibitors with promising clinical benefits.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Chemistry, Inorganic & Nuclear
Darren F. Beirne, Martina Dalla Via, Trinidad Velasco-Torrijos, Diego Montagner
Summary: Tyrosine Kinases play a crucial role in cancer, but small molecule Tyrosine Kinase Inhibitors face limitations in clinical usage. Metal-Tyrosine Kinase Inhibitor conjugates have emerged as a promising area of research to overcome these limitations, with potential applications in multiple biological fields.
COORDINATION CHEMISTRY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Elena V. Koroleva, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Julia V. Siniutsich, Zhanna V. Ignatovich, Alexander M. Andrianov
Summary: An integrated computational approach was used to identify potential inhibitors of Bcr-Abl tyrosine kinase, an enzyme involved in chronic myeloid leukemia. Five compounds were found to effectively block the enzyme activity and exhibit high binding affinity comparable to FDA-approved kinase inhibitors. These compounds may serve as good scaffolds for the design of novel anticancer agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Hematology
Jessica T. Leonard, Yoko Kosaka, Pavani Malla, Dorian LaTocha, Adam Lamble, Brandon Hayes-Lattin, Kaelan Byrd, Brian J. Druker, Jeffrey W. Tyner, Bill H. Chang, Evan Lind
Summary: Combining blinatumomab with different ABL inhibitors in Philadelphia chromosome-positive ALL can have different effects on T-cell proliferation and IFN-gamma production, highlighting the importance of maintaining T-cell function in combination therapies.
Review
Biochemistry & Molecular Biology
Xia-Wen Dang, Ji-Long Duan, Emily Ye, Nian-Dong Mao, Renren Bai, Xinglu Zhou, Xiang-Yang Ye
Summary: This review summarizes the important role of c-Src kinase in cell division, motility, adhesion, and survival, as well as its implications in disease. It provides valuable insights and new ideas for researchers in areas such as inhibitor development, combination therapy, and clinical research.
BIOORGANIC CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Mingxing Teng, Marlise R. Luskin, Sandra W. Cowan-Jacob, Qiang Ding, Doriano Fabbro, Nathanael S. Gray
Summary: This review discusses the recent progress in the treatment of chronic myeloid leukemia (CML) and highlights the discovery and mechanism of action of allosteric inhibitors. The therapeutic potential of these inhibitors in delaying the development of acquired resistance is also explored. The article emphasizes the importance of understanding the fundamental regulatory mechanisms of kinases and presents key lessons learned from this program.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Rajashri R. Naik, Ashok K. Shakya, Safwan M. Aladwan, Mohamed El-Tanani
Summary: The coronavirus is rapidly spreading worldwide, and viral management aims to disrupt the virus's life cycle, minimize lung damage, and alleviate severe symptoms. Various strategies have been implemented, including repurposing FDA-approved kinase inhibitors that have shown antiviral activity against multiple viruses, including those associated with COVID-19.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Tingting Lu, Jiangyan Cao, Fengming Zou, Xixiang Li, Aoli Wang, Wenliang Wang, Huamin Liang, Qingwang Liu, Chen Hu, Cheng Chen, Zhenquan Hu, Wenchao Wang, Lili Li, Jian Ge, Yang Shen, Tao Ren, Jing Liu, Ruixiang Xia, Qingsong Liu
Summary: CHMFL-48 is a novel type II kinase inhibitor that potently inhibits the wild-type BCR-ABL kinase and a panel of imatinib-resistant mutants. This drug shows strong inhibitory activity in a cellular context, blocking autophosphorylation of BCR-ABL kinase, affecting downstream signaling mediators, and inducing cell cycle progression blockade and apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Fanjun Li, Monifa Fahie, Kaitlyn Gilliam, Ryan Pham, Min Chen
Summary: The authors demonstrate that protein nanopore tweezers can be used to analyze the conformational energy landscape and ligand binding of the Abl kinase domain. They identify two major conformational states of the kinase domain and reveal the functional roles of these states in substrate and inhibitor interactions. The results provide insights into the dynamic nature of Abl kinase and suggest that nanopore tweezers can be an efficient tool for studying other members of the human kinome.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Hjalmar Flygt, Fredrik Sandin, Torsten Dahlen, Arta Dremaine, Anna Lubking, Berit Markevarn, Kristina Myhr-Eriksson, Karin Olsson, Ulla Olsson-Stromberg, Anders Sjalander, Stina Soderlund, Lovisa Wennstrom, Hans Wadenvik, Leif Stenke, Martin Hoglund, Johan Richter
Summary: Clinical trials have shown that discontinuing TKI treatment in selected patients with CML is feasible, and this practice is common in clinical settings. The main reasons for stopping TKI treatment are achieving deep molecular response or other specific causes.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Misty M. Attwood, Doriano Fabbro, Aleksandr V. Sokolov, Stefan Knapp, Helgi B. Schioth
Summary: The article analyzes the landscape of approved and investigational therapies that target kinases, highlighting the increasing importance of kinase inhibitors in oncology and beyond. It discusses trends in kinase inhibitor design and points out that there are still substantial unexplored opportunities for this drug class.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Chemistry, Medicinal
You-lu Pan, Shen-xin Zeng, Rong-rong Hao, Mei-hao Liang, Zheng-rong Shen, Wen-hai Huang
Summary: This review summarizes the current research progress of inhibitors and degraders targeting BCR-ABL for the treatment of CML, including first, second, and third-generation tyrosine kinase inhibitors targeting different mutations, as well as allosteric inhibitors and proteolysis-targeting chimeras (PROTAC) based on different E3 ligands.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Yu Zhou, Xin Li, Ru Shen, Xiangzhu Wang, Fan Zhang, Suxing Liu, Di Li, Jian Liu, Puhui Li, Yinfa Yan, Ping Dong, Zhigao Zhang, Heping Wu, Linghang Zhuang, Rasheduzzaman Chowdhury, Matthew Miller, Mena Issa, Yuchang Mao, Hongli Chen, Jun Feng, Jing Li, Chang Bai, Feng He, Weikang Tao
Summary: TYK2 is a crucial member of the JAK family, playing an important role in mediating cytokine-signaling pathways and contributing to autoimmune disorders. In this study, small-molecule TYK2 pseudokinase ligands were developed to suppress TYK2 catalytic activity through allosteric regulation, which could be potential therapeutics for cytokine-driven inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Paulo Ricardo Criado, Daniel Lorenzini, Helio Amante Miot, Roberto Bueno-Filho, Francisca Regina Oliveira Carneiro, Mayra Ianhez
Summary: This article provides an overview of a new class of drugs that can block important intracellular signaling pathways, thereby treating inflammatory, autoimmune, genetic, and neoplastic diseases. These drugs have significant implications for the treatment of dermatological diseases.
INFLAMMATION RESEARCH
(2023)