Review
Chemistry, Medicinal
Ricardo Moreno, Javier Recio, Santiago Barber, Carmen Gil, Ana Martinez
Summary: Selective and brain-permeable protein kinase inhibitors, particularly MLK3 inhibitors, have shown potential for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis. These inhibitors have demonstrated strong neuroprotective effects and some have even reached clinical trials. This review focuses on the role of MLK3 in neuron-related cell death processes, neurodegenerative diseases, and the potential benefits of targeting this kinase for neuroprotective treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Swapnil P. Bhujbal, Jung-Mi Hah
Summary: Due to dysregulation of protein kinase activity, the protein kinase family has become a crucial drug target in various diseases. Covalent inhibitors have shown significant advancements in cancer treatment, but their potential in neurodegenerative diseases remains largely unexplored.
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Dominika Natalia Wojewska, Arjan Kortholt
Summary: This review provides a comprehensive overview of the current state of the art, presenting recent developments and challenges in developing LRRK2 inhibitors, and discussing extensively the potential targeting strategies from the protein perspective. As currently there are three LRRK2-targeting agents in clinical trials, more developments are predicted in the upcoming years.
Article
Chemistry, Multidisciplinary
Eleanor L. Atkinson, Jessica Iegre, Claudio D'Amore, Paul Brear, Mauro Salvi, Marko Hyvonen, David R. Spring
Summary: In this study, an iterative cycle of enzymatic assays, X-ray crystallography, molecular modelling and cellular assays was used to develop a functionalisable chemical probe for the investigation of CK2α/β PPI. The lead peptide, P8C9, showed successful binding to CK2α at the PPI site, and it was found to be easily synthesizable and functionalisable. The peptide also exhibited high stability in serum and had potential for further optimization.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Zhouling Xie, Xiaoxiao Yang, Yajun Duan, Jihong Han, Chenzhong Liao
Summary: Kinase inhibitors have been successful in treating various diseases beyond cancer, including autoimmune diseases and inflammatory diseases. Several non-oncologic small-molecule kinase inhibitors have been approved, with more in development for different applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rashid Waseem, Saleha Anwar, Shama Khan, Anas Shamsi, Md. Imtaiyaz Hassan, Farah Anjum, Alaa Shafie, Asimul Islam, Dharmendra Kumar Yadav
Summary: The study demonstrates that irisin binds to MARK4 and inhibits its activity, providing a new therapeutic approach for MARK4-associated diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Adriano Brescacin, Zunaira Baig, Jaspreet Bhinder, Sen Lin, Lovejot Brar, Nicola Cirillo
Summary: This article systematically evaluates the role of kinases in pemphigus vulgaris (PV) and finds evidence that kinase inhibition reduces PV-related pathological events and blocks blister formation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rongsheng Xu, Huidan Tan, Jiahui Zhang, Zhaoxin Yuan, Qiang Xie, Lan Zhang
Summary: Fam20C, a Golgi casein kinase, is associated with Raine Syndrome and plays a crucial role in biological functions by phosphorylating secreted proteins. Its potential in enhancing cancer metastasis has led to the investigation of small-molecule inhibitors for therapeutic purposes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Editorial Material
Pharmacology & Pharmacy
Marco P. Licciardello, Paul Workman
Summary: Casein kinase 2, a potential therapeutic target in cancer due to its high expression, did not exhibit broad antiproliferative activity in cancer cells when targeted by the new inhibitor SGC-CK2-1, developed by Wells and colleagues.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Review
Chemistry, Medicinal
Giusy Tassone, Marco Mazzorana, Cecilia Pozzi
Summary: Protozoan parasites are responsible for harmful diseases in humans, and new specific drug therapies are urgently needed. HSP90 plays a key role in parasite survival, with the N-terminal domain being a crucial target for inhibitor development.
Article
Biochemistry & Molecular Biology
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. A. Pinna
Summary: CK2 is a Ser/Thr protein kinase that is often highly active in cancer cells. Knock-out myoblast clones of CK2 alpha/alpha ' still express a deleted alpha ' subunit, which challenges the idea that CK2 may be dispensable for cell survival. Although the overall CK2 activity of these cells is significantly lower than wild-type cells, the number of phosphosites with the CK2 consensus is comparable. However, further analysis reveals that the two phosphoproteomes are not identical, indicating that minimal CK2 activity is sufficient for basic functions but not for specialized tasks.
Article
Chemistry, Medicinal
Agnieszka Dreas, Katarzyna Kucwaj-Brysz, Karolina Pyziak, Urszula Kulesza, Ewelina Wincza, Charles-Henry Fabritius, Kinga Michalik, Ewelina Gabor-Worwa, Aniela Golas, Mariusz Milik, Magdalena Masiejczyk, Eliza Majewska, Kazimiera Pysniak, Urszula Wojcik-Trechcinska, Zuzanna Sandowska-Markiewicz, Krzysztof Brzozka, Jerzy Ostrowski, Tomasz Rzymski, Michal Mikula
Summary: The study suggests that inhibition of the MNKs/eIF4E pathway can potentially treat cancer and inflammatory diseases. Compounds 24 and 26, selective and metabolically stable MNK1/2 inhibitors, effectively reduce the phosphorylation levels of eIF4E in pathological conditions, leading to improved survival rates and reduced proinflammatory cytokine levels in mice models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Alexander Schnitzler, Karsten Niefind
Summary: CK2, a Ser/Thr kinase, has a specific acidic substrate recognition sequence and is inhibited by polyanionic substances like heparin. This study describes the crystal structures of CK2 in complex with different heparin fragments, which provide insights into the inhibitory mechanism of heparin fragments and their chain length-dependent efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Edgar Carnero Contentti, Jorge Correale
Summary: Multiple sclerosis is a chronic inflammatory disease of the central nervous system. B cells and myeloid cells play key roles in the development of the disease. BTK inhibitors show promise as novel therapeutic approaches for multiple sclerosis.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)