Article
Biochemistry & Molecular Biology
Betheney R. Pennycook, Alexis R. Barr
Summary: The use of CDK4/6 inhibitors in cancer treatment is a topic of ongoing investigation, with limited understanding of their mechanisms of action. Recent data have raised questions about how these inhibitors arrest cell proliferation, leading to renewed interest in the roles of CDK4/6. Studying the effects of CDK4/6 inhibitors on the cell cycle can have implications for cancer treatment and patient stratification.
Review
Oncology
Alessandra Merlini, Valeria Pavese, Giulia Manessi, Martina Rabino, Francesco Tolomeo, Sandra Aliberti, Lorenzo D'Ambrosio, Giovanni Grignani
Summary: Effective treatment of advanced/metastatic bone and soft tissue sarcomas remains a medical challenge. CDK inhibitors have shown potential therapeutic effects in various cancer types, including sarcomas. This review explores the molecular basis and therapeutic implications of CDK inhibitors in sarcoma treatment and discusses the possibility of combination therapies with conventional treatments, targeted therapy, and immunotherapy to integrate CDK inhibition in sarcoma treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Oncology
Mitra Zabihi, Ramin Lotfi, Amir-Mohammad Yousefi, Davood Bashash
Summary: CDKs, cyclins, and CKIs play important roles in the cell cycle regulatory machinery, and dysregulation of their expression or function can contribute to tumorigenesis. While designing CDK inhibitors to target tumor cells shows promise, the non-canonical functions of CDKs pose challenges in their application. This review aims to explore the biology of CDKs and their contribution to tumorigenesis, and discuss the pros and cons of CDK inhibition in the treatment of human cancers.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Oana-Maria Thoma, Markus F. Neurath, Maximilian J. Waldner
Summary: CDKs play a key role in cell cycle regulation, with aberrant expression potentially leading to cancer development. CDK inhibitors, such as CDK4/6 inhibitors, are being investigated as novel cancer therapies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Omchit Surien, Ahmad Rohi Ghazali, Siti Fathiah Masre
Summary: This study demonstrates that pterostilbene can inhibit proliferation and promote apoptosis of lung squamous cell carcinoma cells by regulating the cell cycle and upregulating the p53/p21 pathway.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Aadil Javed, Mahdieh Yarmohammadi, Kemal Sami Korkmaz, Teresa Rubio-Tomas
Summary: Gastric cancer is characterized by uncontrolled growth and metastasis of gastric epithelial cells, which is predominantly in adenocarcinoma form. The regulation of gastric cell growth is influenced by key cell cycle regulators, including Cyclins and Cyclin-dependent kinases (CDKs). Dysregulation of these molecules can lead to disturbances in cell cycle dynamics and the development of gastric cancer. Numerous studies have examined the roles of Cyclins and CDKs in gastric cancer, and this review aims to compile evidence of upstream regulators that activate or inhibit Cyclins and CDKs. It serves as a comprehensive resource for future studies and hypothesis generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Peixin Dong, Nikolaus Gassler, Mohammad Taheri, Aria Baniahmad, Nader Akbari Dilmaghani
Summary: This article summarizes the important role of Cyclin-dependent kinases (CDK) in cancer, emphasizing the significance of understanding CDK function and mechanisms for future cancer therapies targeting these kinases.
CANCER CELL INTERNATIONAL
(2022)
Article
Microbiology
Chonglv Feng, Zhe Cheng, Zhijian Xu, Ye Tian, Huimin Tian, Fan Liu, Damin Luo, Yanhai Wang
Summary: This study describes the cell cycle regulation mechanism of germinative cells in the tapeworm Echinococcus multilocularis, which is influenced by the interaction between the parasite and the host. Host EGF regulates the G1/S phase of the cell cycle through the EGFR-ERK-EmCyclinD pathway.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biology
Mohamed A. Elkady, Ahmed S. Doghish, Ahmed Elshafei, Mostafa M. Elshafey
Summary: miR-567 is downregulated in A549 NSCLC cells, but its upregulation can inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, and act as a tumor suppressor by regulating CDK8 gene expression.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Minhui Yang, Changxiao Hu, Yibo Cao, Wanling Liang, Xiangdong Yang, Tianbao Xiao
Summary: The study explores the biological functions of CCNB1 in COAD and investigates the therapeutic effects of UA on COAD cells. UA effectively inhibits COAD cell proliferation and induces cell cycle arrest in S phase. The molecular mechanisms of UA involve downregulation of CCNB1 and its interacting genes and proteins, contributing to cell cycle blocking and COAD treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jorrit M. Enserink, Pierre Chymkowitch
Summary: Cdk1 is a master regulator of the cell cycle, controlling progression through different phases. It also directly regulates RNA polymerase activity, which is important for protein synthesis and meeting cellular demands. This regulation promotes cell cycle entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Riham R. E. Abouleisa, Jessica M. Miller, Ahmad Gebreil, Abou Bakr M. Salama, Marc Dwenger, Hania Abdelhafez, Reham M. Wahid, Adeniyi T. Adewumi, Mahmoud E. S. Soliman, Nader E. Abo-Dya, Tamer M. A. Mohamed
Summary: This study identified a small molecule called NDPPC, which can enhance the cell cycle progression of cardiomyocytes and has the potential to be a drug for heart failure treatment.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jingshan Tong, Xiao Tan, Suisui Hao, Kaylee Ermine, Xinyan Lu, Zhaojin Liu, Anupma Jha, Jian Yu, Lin Zhang
Summary: Targeting cyclin-dependent kinases (CDKs) has shown promising therapeutic potential against cancer. A recent study reveals that selective CDK4/6 inhibitors induce Death Receptor 5 (DR5) via p73, leading to increased sensitivity of colorectal cancer cells to therapy-induced apoptosis. This finding provides valuable insights into the anticancer mechanisms of CDKIs and their potential clinical applications in colorectal cancer.
Article
Chemistry, Inorganic & Nuclear
Ruilin Guan, Lina Xie, Lili Wang, Ying Zhou, Yu Chen, Liangnian Ji, Hui Chao
Summary: NecroIr1 and NecroIr2, iridium(iii) complexes, induce necroptosis in cisplatin-resistant lung cancer cells by selectively accumulating in mitochondria and causing oxidative stress. Additionally, they interfere with cell cycle progression, leading to G0/G1 phase arrest. The combined effect of necroptosis induction and cell cycle arrest makes them potential antitumor agents against drug-resistant cancer cells.
INORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Cell Biology
Thomas A. Natoli, Vijay Modur, Oxana Ibraghimov-Beskrovnaya
CELLULAR SIGNALLING
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Priyanka Gupta, Keehn Strange, Angela Carter, Rahul Telenge, Laurent Meijer, Hans Ghayee, Karel Pacak, Sushanth Reddy, James Bibb
Article
Biochemistry & Molecular Biology
Herve Husson, Nikolay O. Bukanov, Sarah Moreno, Mandy M. Smith, Brenda Richards, Cheng Zhu, Tyler Picariello, Hyejung Park, Bing Wang, Thomas A. Natoli, Laurie A. Smith, Stefano Zanotti, Ryan J. Russo, Stephen L. Madden, Katherine W. Klinger, Vijay Modur, Oxana Ibraghimov-Beskrovnaya
HUMAN MOLECULAR GENETICS
(2020)
Article
Oncology
Amriti R. Lulla, Said Akli, Cansu Karakas, Min Jin Ha, Natalie W. Fowlkes, Yoshitsugu Mitani, Tuyen Bui, Jing Wang, Xiayu Rao, Kelly K. Hunt, Laurent Meijer, Adel K. El-Naggar, Khandan Keyomarsi
Summary: This study established a novel transgenic mouse model efficiently recapitulating the major histological subtype of human SGC. LMW-E was found to preferentially bind to CDK5 in the absence of CDK2. Clinical evidence showed that co-expression of LMW-E/CDK5 was significantly associated with decreased recurrence free survival in human SGC.
Review
Biochemistry & Molecular Biology
Mattias F. Lindberg, Laurent Meijer
Summary: DYRK and CLK kinases are involved in various cellular functions and their abnormal expression/activity are linked to multiple neurological diseases, cancers, and other conditions. Research on the regulation of these kinases and the development of inhibitors is crucial for the treatment of related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Respiratory System
Laurent Meijer, Genevieve Hery-Arnaud, Cyril Leven, Emmanuel Nowak, Sophie Hillion, Yves Renaudineau, Isabelle Durieu, Raphael Chiron, Anne Prevotat, Isabelle Fajac, Dominique Hubert, Marlene Murris-Espin, Sandrine Huge, Isabelle Danner-Boucher, Bruno Ravoninjatovo, Sylvie Leroy, Julie Macey, Thierry Urban, Gilles Rault, Dominique Mottier, Rozenn Le Berre
Summary: A study was conducted to evaluate the safety and effects of roscovitine in patients with Cushing disease. The results showed that roscovitine was relatively safe and well-tolerated, but did not show significant efficacy in treating the disease. The variability in pharmacokinetics of roscovitine may have contributed to the lack of effectiveness.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Chemistry, Medicinal
Tania Tahtouh, Emilie Durieu, Benoit Villiers, Celine Bruyere, Thu Lan Nguyen, Xavier Fant, Kwang H. Ahn, Leepakshi Khurana, Emmanuel Deau, Mattias F. Lindberg, Elodie Severe, Frederic Miege, Didier Roche, Emmanuelle Limanton, Jean-Martial L'helgoual'ch, Guillaume Burgy, Solene Guiheneuf, Yann Herault, Debra A. Kendall, Francois Carreaux, Jean-Pierre Bazureau, Laurent Meijer
Summary: Leucettines, derived from marine sponge alkaloid Leucettamine B, have potential therapeutic applications for Alzheimer's disease, Down syndrome, diabetes, and other diseases. There is a correlation between the inhibition of specific kinase targets and cellular effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Khadidja Bourahla, Solene Guiheneuf, Emmanuelle Limanton, Ludovic Paquin, Remy Le Guevel, Thierry Charlier, Mustapha Rahmouni, Emilie Durieu, Olivier Lozach, Francois Carreaux, Laurent Meijer, Jean-Pierre Bazureau
Summary: A method for synthesizing new compounds was reported, and their activity against protein kinases as well as inhibition of tumor cell proliferation was tested. Two compounds were identified as potential DYRK1A inhibitors, offering new directions for drug development in neurological or oncological disorders.
Article
Clinical Neurology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
Summary: The presence of both soluble forms of Aβ 342 and p-tau may be responsible for the onset of mild cognitive impairment (MCI) in Alzheimer's disease (AD).
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Cell Biology
Priyanka Gupta, Keehn Strange, Rahul Telange, Ailan Guo, Heather Hatch, Amin Sobh, Jonathan Elie, Angela M. Carter, John Totenhagen, Chunfeng Tan, Yogesh A. Sonawane, Jiri Neuzil, Amarnath Natarajan, Ashley J. Ovens, Jonathan S. Oakhill, Thorsten Wiederhold, Karel Pacak, Hans K. Ghayee, Laurent Meijer, Sushanth Reddy, James A. Bibb
Summary: Metabolic dysfunction mutations can lead to cancer. Loss of SDHB triggers a signaling cascade that disrupts energy sensing and promotes cancer progression.
Review
Biochemistry & Molecular Biology
Yashoda Krishna Sunkari, Laurent Meijer, Marc Flajolet
Summary: Protein kinases are essential in biology and their deregulation is linked to various diseases. However, the high conservation of ATP-binding sites among kinases makes it challenging to develop highly specific inhibitors. In the context of neurodegenerative diseases, CK1 and other kinases have been implicated. Currently, there are no specific regulators for CK1, and known inhibitors target the ATP-binding site. DNA-encoded library technology may be a promising approach to discover allosteric modulators instead of ATP competitors.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Medicinal
Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas George, Pascal George, Patricia Alfonso, Ana Corrionero, Laurent Meijer
Summary: This study evaluates the kinase inhibitory activity of a library of DYRKs/CLKs inhibitors and finds a diverse range of potencies and selectivities among these inhibitors, highlighting the challenges of targeting kinases in this area of research. The use of a panel of inhibitors is suggested for studying the functions of these kinases in cellular processes.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emmanuel Deau, Mattias F. F. Lindberg, Freideiric Miege, Didier Roche, Nicolas George, Pascal George, Andreas Kra''mer, Stefan Knapp, Laurent Meijer
Summary: Dual-specificity,tyrosine phosphorylation-regulated kinases (DYRKs) and cdc2-like kinases (CLKs) have been identified as important targets for various pathologies. In this study, a family of DYRK/CLK inhibitors called Leucettinibs, derived from Leucettines and Leucettamine B, were synthesized and characterized. These inhibitors showed subnanomolar IC50 on DYRK1A and demonstrated potential for therapeutic drug development. Kinase-inactive isomers, iso-Leucettinibs, were also synthesized as suitable negative control compounds. Leucettinibs were found to inhibit DYRK1A substrate phosphorylation in cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Correction
Clinical Neurology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Correction
Geriatrics & Gerontology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JOURNAL OF NUTRITION HEALTH & AGING
(2022)