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
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)
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)
Article
Chemistry, Multidisciplinary
Bohan Ma, Hui Feng, Chao Feng, Yi Liu, Hailing Zhang, Jincheng Wang, Wenjuan Wang, Pengcheng He, Fan Niu
Summary: The study designed a dual-targeting proteolysis-targeting chimera (PROTAC) type drug that can induce Bcr/Abl degradation and activate the p53 pathway simultaneously, potentially overcoming drug resistance in Ph+ leukemias.
Article
Oncology
Charlotte E. J. Downes, Barbara J. McClure, John B. Bruning, Elyse Page, James Breen, Jacqueline Rehn, David T. Yeung, Deborah L. White
Summary: The study demonstrates that the JAK2 p.G993A mutation can confer resistance to multiple JAK inhibitors by modulating the mobility of the JAK2 activation loop, providing insights for future drug design and therapeutic strategies in high-risk patients with JAK2-rearranged B-cell acute lymphoblastic leukemia.
NPJ PRECISION ONCOLOGY
(2021)
Review
Oncology
Nicholas J. Short, Hagop Kantarjian, Elias Jabbour
Summary: With the introduction of highly potent BCR-ABL tyrosine kinase inhibitors, the risk of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has been reduced, and new chemotherapy-free regimens are showing promising results. These regimens may become the new standard of care for Ph+ ALL patients.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(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
Pediatrics
Shuvadeep Ganguly, Archana Sasi, Deepam Pushpam, Sameer Bakhshi
Summary: This article describes the diagnosis and treatment methods of Philadelphia chromosome positive acute lymphoblastic lymphoma (Ph+ ALL) in children, including conventional karyotyping and BCR-ABL1 translocation detection, as well as using chemotherapy and hematopoietic stem cell transplantation to control and treat the disease.
INDIAN JOURNAL OF PEDIATRICS
(2023)
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
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)
Article
Medicine, Research & Experimental
Zhuo-Xun Wu, Qiuyan Mai, Yuqi Yang, Jing-Quan Wang, Hansu Ma, Leli Zeng, Zhe-Sheng Chen, Yihang Pan
Summary: Overexpression of ABCG2 transporter leads to resistance of cancer cells to GSK1070916, and combination with an ABCG2 inhibitor can restore the sensitivity of GSK1070916.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Pelin Ayaz, Agatha Lyczek, YiTing Paung, Victoria R. Mingione, Roxana E. Iacob, Parker W. de Waal, John R. Engen, Markus A. Seeliger, Yibing Shan, David E. Shaw
Summary: The authors used molecular dynamics simulations to study the binding process of Abl kinase with the cancer drug imatinib. The simulations revealed that imatinib induces a large conformational change of the protein and identified a region in Abl kinase that is structurally unstable during binding. Mutations in this region confer imatinib resistance by exacerbating structural instability.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Haixia Liu, Qianglong Mi, Xinyu Ding, Chencen Lin, Linyi Liu, Chaowei Ren, ShuTing Shen, YuBao Shao, Jinju Chen, Yongqi Zhou, Liting Ji, Heqiao Zhang, Fang Bai, Xiaobao Yang, Qianqian Yin, Biao Jiang
Summary: In this study, a novel series of CRBN-recruiting proteolysis-targeting chimeras (PROTACs) targeting BCR-ABL were synthesized, and compound 30 (SIAIS100) was discovered to be the most potent degrading agent against BCR-ABL. The compound exhibited sustained efficacy for 96 hours post-washout and showed degradative activity against various clinically relevant resistance-conferring mutations of BCR-ABL.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Chang Liu, Waiyi Zou, Danian Nie, Shuyi Li, Chen Duan, Min Zhou, Peilong Lai, Shengyong Yang, Sen Ji, Yangqiu Li, Mei Mei, Shilai Bao, Yanli Jin, Jingxuan Pan
Summary: This study investigates the role of PRMT family member PRMT7 in the maintenance of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). The research shows that targeting PRMT7 delays leukemia development and impairs self-renewal of LSCs without affecting normal hematopoiesis. Mechanistically, loss of PRMT7 leads to reprogramming of glycine metabolism, generating methylglyoxal which is detrimental to LSCs. These findings suggest PRMT7 as a potential therapeutic target for eradicating LSCs in CML.
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
Oncology
Irina Sadovnik, Andrea Hoelbl-Kovacic, Harald Herrmann, Gregor Eisenwort, Sabine Cerny-Reiterer, Wolfgang Warsch, Gregor Hoermann, Georg Greiner, Katharina Blatt, Barbara Peter, Gabriele Stefanzl, Daniela Berger, Martin Bilban, Susanne Herndlhofer, Heinz Sill, Wolfgang R. Sperr, Berthold Streubel, Christine Mannhalter, Tessa L. Holyoake, Veronika Sexl, Peter Valent
CLINICAL CANCER RESEARCH
(2016)
Article
Immunology
Milica Vukovic, Amelie V. Guitart, Catarina Sepulveda, Arnaud Villacreces, Eoghan O'Duibhir, Theano I. Panagopoulou, Alasdair Ivens, Juan Menendez-Gonzalez, Juan Manuel Iglesias, Lewis Allen, Fokion Glykofrydis, Chithra Subramani, Alejandro Armesilla-Diaz, Annemarie E. M. Post, Katrin Schaak, Deniz Gezer, Chi Wai Eric So, Tessa L. Holyoake, Andrew Wood, Donal O'Carroll, Peter J. Ratcliffe, Kamil R. Kranc
JOURNAL OF EXPERIMENTAL MEDICINE
(2015)
Article
Oncology
M. Schemionek, O. Herrmann, M. M. Reher, N. Chatain, C. Schubert, I. G. Costa, S. Haenzelmann, E. G. Gusmao, S. Kintsler, T. Braunschweig, A. Hamilton, G. V. Helgason, M. Copland, A. Schwab, C. Mueller-Tidow, S. Li, T. L. Holyoake, T. H. Bruemmendorf, S. Koschmieder
Article
Cell Biology
Maria Karvela, Pablo Baquero, Elodie M. Kuntz, Arunima Mukhopadhyay, Rebecca Mitchell, Elaine K. Allan, Edmond Chan, Kamil R. Kranc, Bruno Calabretta, Paolo Salomoni, Eyal Gottlieb, Tessa L. Holyoake, G. Vignir Helgason
Article
Hematology
Milica Vukovic, Catarina Sepulveda, Chithra Subramani, Amelie V. Guitart, Jasmine Mohr, Lewis Allen, Theano I. Panagopoulou, Jasmin Paris, Hannah Lawson, Arnaud Villacreces, Alejandro Armesilla-Diaz, Deniz Gezer, Tessa L. Holyoake, Peter J. Ratcliffe, Kamil R. Kranc
Article
Multidisciplinary Sciences
Sheela A. Abraham, Lisa E. M. Hopcroft, Emma Carrick, Mark E. Drotar, Karen Dunn, Andrew J. K. Williamson, Koorosh Korfi, Pablo Baquero, Laura E. Park, Mary T. Scott, Francesca Pellicano, Andrew Pierce, Mhairi Copland, Craig Nourse, Sean M. Grimmond, David Vetrie, Anthony D. Whetton, Tessa L. Holyoake
Article
Multidisciplinary Sciences
David A. Irvine, Bin Zhang, Ross Kinstrie, Anuradha Tarafdar, Heather Morrison, Victoria L. Campbell, Hothri A. Moka, Yinwei Ho, Colin Nixon, Paul W. Manley, Helen Wheadon, John R. Goodlad, Tessa L. Holyoake, Ravi Bhatia, Mhairi Copland
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Elodie M. Kuntz, Pablo Baquero, Alison M. Michie, Karen Dunn, Saverio Tardito, Tessa L. Holyoake, G. Vignir Helgason, Eyal Gottlieb
Meeting Abstract
Hematology
A. M. Michie, A. Tarafdar, P. Gallipolli, F. Pellicano, L. Hopcroft, K. Korfi, J. Cassels, H. J. Jorgensen, D. Vetrie, T. L. Holyoake
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Meeting Abstract
Hematology
L. Mukherjee, S. Rankin, A. Laird, Y-C Hsieh, L. E. M. Hopcroft, E. K. Allan, I. Ben Batalla, D. Micklem, T. L. Holyoake, S. Loges, H. G. Jorgensen
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Meeting Abstract
Hematology
L. Jackson, L. E. M. Hopcroft, S. Rogers, H. Jorgensen, F. Pellicano, C. Wells, R. Mosbergen, T. Chen, D. Vetrie, T. L. Holyoake
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Meeting Abstract
Hematology
E. Gomez-Castaneda, L. E. M. Hopcroft, S. Rogers, H. G. Jorgensen, F. Pellicano, D. Vetrie, M. Copland, S. Grimmond, T. L. Holyoake
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Meeting Abstract
Hematology
Alexander M. Labeit, Mhairi Copland, Leanne M. Cork, Corinne A. Hedgley, Letizia Foroni, Wendy L. Osborne, Gemma Gills, Jane F. Apperley, Tessa L. Holyoake, Ruth V. Bescoby, Christopher Pocock, Thomas Zwingers, Philippa Burnell, Jenny L. Byrne, John H. McCullough, John M. Goldman, Richard E. Clark, Stephen G. O'Brien
Meeting Abstract
Hematology
Jacqueline Dickson, Nick Kennedy, Leanne M. Cork, Letizia Foroni, Corinne A. Hedgley, Mhairi Copland, Tessa L. Holyoake, Stephen G. O'Brien, Bernard Ramashoye
Meeting Abstract
Hematology
F. E. Nicolini, D. J. DeAngelo, E. Abruzzese, J. F. Apperley, T. L. Holyoake, R. A. Larson, S. Lustgarten, V. M. Rivera, T. Clackson, M. G. Conlan, F. G. Haluska, M. Talpaz, J. E. Cortes