Review
Chemistry, Medicinal
Mohamed A. Said, Mohamed A. Abdelrahman, Mohammed A. S. Abourehab, Mohamed Fares, Wagdy M. Eldehna
Summary: Developing selective CDK2 inhibitors is challenging, but ongoing efforts by Incyte Corporation and Pfizer Inc. may bring novel information critical for the development of CDK2 inhibitors.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Article
Cell Biology
Sargun Sokhi, Cody W. Lewis, Amirali B. Bukhari, Joanne Hadfield, Edric J. Xiao, Jeremy Fung, Yea Jin Yoon, Wen-Hsin Hsu, Armin M. Gamper, Gordon K. Chan
Summary: Cell cycle checkpoint kinases are important targets for cancer therapy, and their inhibition can induce cell death or increase sensitivity to other genotoxic therapies. In this study, the researchers found that the overexpression of Myt1, a kinase regulating cell cycle progression, confers resistance to inhibitors of other kinases. Elevated Myt1 levels compensate for Cdk1 inhibition and lead to reduced premature mitotic entry and decreased length of mitosis, ultimately increasing cell survival rates. The findings suggest that Myt1 overexpression is a common mechanism by which cancer cells acquire resistance to drugs targeting the G2/M checkpoint.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Natalie Oberhuber, Hindole Ghosh, Bianca Nitzsche, Prasad Dandawate, Michael Hoepfner, Rainer Schobert, Bernhard Biersack
Summary: New N-alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles and their (p-cymene)Ru(II) piano-stool complexes were synthesized and found to exhibit potent antiproliferative activity in various cancer models. Some of the derivatives showed lower IC50 values than clinically relevant multikinase inhibitors gefitinib and sorafenib, indicating their potential as novel therapeutic agents for cancer treatment. The investigation of drug mechanism in HCT-116 p53-knockout colon cancer cells revealed that the derivatives induced apoptotic caspase-3/7 activity, ROS formation, and anti-angiogenic properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Motahareh Mortazavi, Elaheh Raufi, Tahereh Damghani, Mehdi Khoshneviszadeh, Najmeh Edraki, Masoomeh Eskandari, Elisa Giovannetti, Godefridus J. Peters, Somayeh Pirhadi, Omidreza Firuzi
Summary: c-Met receptor tyrosine kinase is an important therapeutic target in pancreatic cancer. A virtual screening and experimental testing were conducted to identify potential c-Met inhibitors from a compound library. The most active compound, PhTH, demonstrated antiproliferative effects against PDAC cells, induced apoptosis, and inhibited c-Met activity. Molecular docking and simulation analysis confirmed the strong interactions between PhTH and c-Met kinase domain. These findings suggest the potential of PhTH and other compounds as c-Met inhibitors in the treatment of PDAC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Chemistry, Medicinal
Ting Guo, Shutao Ma
Summary: The treatment of cancer faces challenges with currently approved tyrosine kinase inhibitors, as they are becoming less effective in complex cancers and contributing to chemotherapy resistance. Multitargeted tyrosine kinase inhibitors are more advantageous in therapeutic effects and have become a hotspot in antitumor drug research.
Review
Pharmacology & Pharmacy
Puhua Wu, Yan Zhou, Yizhen Guo, Shao-Lin Zhang, Kin Yip Tam
Summary: MCTs play a crucial role in lactate/proton efflux and may serve as a new target for anticancer therapies. While X-ray co-crystal structures of human MCTs with inhibitors are unavailable, homology models have aided in the design of new MCT inhibitors. Future directions include studying the structures and functions of MCT inhibitors and discovering more small-molecule inhibitors.
DRUG DISCOVERY TODAY
(2021)
Review
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Fatemeh Emadi, Jimma Lenjisa, Laychiluh Mekonnen, Shudong Wang
Summary: As the fifth pillar of cancer treatment, immunotherapy has revolutionized therapeutic strategies by focusing on the host's immune system. The discovery of immune-modulatory effects for kinase inhibitors has opened up new possibilities in this approach, as these small molecule inhibitors not only directly target essential proteins for tumor survival and proliferation, but also stimulate immune responses against malignant cells.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Multidisciplinary
Aysha Gaur, Mudasir Nabi Peerzada, Nashrah Sharif Khan, Imran Ali, Amir Azam
Summary: A series of novel indole based sulfonohydrazide derivatives containing morpholine heterocyclic ring were synthesized and evaluated for their anticancer activity. Compound 5f showed promising inhibition of breast cancer cells and was found to be non-toxic to noncancerous cells.
Article
Biochemistry & Molecular Biology
Prasenjit Mondal, Saswat Mohapatra, Debmalya Bhunia, Prabir Kumar Gharai, Nabanita Mukherjee, Varsha Gupta, Satyajit Ghosh, Surajit Ghosh
Summary: Cell proliferation is a crucial step that may lead to cancer if not properly regulated, with p16 protein often remaining inactive in cancer cells. Researchers have focused on restoring the activity of p16 protein using new viral vectors, small molecules, and peptides to control abnormal cell proliferation. By conjugating a nuclear-localized signal (NLS) sequence and a short peptide (AVPI), the efficiency of p16 peptide as an anti-leukemia therapeutic agent has been significantly enhanced.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Motahareh Mortazavi, Masoumeh Divar, Tahereh Damghani, Fatemeh Moosavi, Luciano Saso, Somayeh Pirhadi, Mehdi Khoshneviszadeh, Najmeh Edraki, Omidreza Firuzi
Summary: In this study, a series of novel quinazolinone hydrazide triazole derivatives were designed and synthesized as MET receptor tyrosine kinase inhibitors. Compound CM9 showed significant antiproliferative effect and apoptosis induction in lung cancer cells, and also inhibited several other protein kinases.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Alexander Kastner, Theresa Mendrina, Florian Bachmann, Walter Berger, Bernhard K. Keppler, Petra Heffeter, Christian R. Kowol
Summary: In this study, oxaliplatin(iv)-based complexes were developed as platinum(iv) prodrugs to release aspirin, which has shown antitumor activity against colon cancer. The newly synthesized complex demonstrated increased reduction stability compared to a cisplatin analog and exhibited desired prodrug properties in cell culture. A derivative with albumin-binding properties showed improved pharmacokinetics and tumor accumulation, leading to enhanced antitumor activity and overall survival in tumor-bearing mice.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Nadia A. Khalil, Eman M. Ahmed, Ashraf F. Zaher, Shimaa M. Alhamaky, Nada Osama, Mona S. El-Zoghbi
Summary: New benzothienopyran and benzothienopyranopyrimidine derivatives were synthesized as potential topoisomerase I inhibitors, exhibiting strong cytotoxic activity against human tumor cell lines. Eight compounds demonstrated broad spectrum and potent anticancer efficacy, while three compounds showed excellent inhibitory activity in DNA relaxation assay. Compound 4d arrested cell growth at S phase and demonstrated similar binding pattern to indenoisoquinoline reference drug, indicating its potential as a Topo I inhibitor.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Moataz A. Shaldam, Denisa Hendrychov, Radwan El-Haggar, Veronika Voj, Taghreed A. Majrashi, Eslam B. Elkaeed, Nicolas Masurier, Vladimir Krystof, Haytham O. Tawfik, Wagdy M. Eldehna
Summary: A study reports the development of novel derivatives of pyrimido[1,2-a]benzimidazole as potential anti-AML agents. Compound 5h exhibited effective anti-tumor activity at low micromolar concentration, particularly against leukemia. Furthermore, compounds 5e-h showed single-digit micromolar activity against acute leukemia cell lines. Pyrimido[1,2-a]benzimidazoles 5e and 5h significantly inhibited BMX kinase.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Gaby A. M. Eliesen, Hedwig van Hove, Maartje H. Meijer, Petra H. H. van den Broek, Jeanne Pertijs, Nel Roeleveld, Joris van Drongelen, Frans G. M. Russel, Rick Greupink
Summary: The study aimed to compare the effects of various anticancer drugs on viability and steroidogenesis in placental tissue explants and trophoblast cell lines. Most anticancer drugs affected viability significantly in both placental explants and trophoblast cell lines, highlighting the placenta as a potential target organ for toxicity of these drugs. The results suggest the importance of studying placental toxicity of anticancer drugs during pregnancy.
ARCHIVES OF TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Manzar Alam, Md. Meraj Ansari, Saba Noor, Taj Mohammad, Gulam Mustafa Hasan, Syed Naqui Kazim, Md. Imtaiyaz Hassan
Summary: TBK1 plays a fundamental role in regulating cellular responses and controlling signaling cascades. Dysregulation of the TBK1 pathway is associated with various pathophysiological conditions. Inhibitors targeting TBK1 have potential therapeutic applications for diseases, including cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Hematology
Silje Johansen, Ingvild Jenssen Laegreid, Siw Leiknes Ernstsen, Nessar Ahmad Azrakhsh, Astrid Olsnes Kittang, Roald Lindas, Bjorn Tore Gjertsen, Nils Vetti, Trude Victoria Mortberg, Ingvild Hausberg Sorvoll, Pal Andre Holme, Maria Therese Ahlen, Hakon Reikvam
Summary: This study reported a case of VITT following HPV vaccination, suggesting the possibility of VITT occurring after other vaccines, not limited to adenoviral vector-based SARS-CoV-2 vaccines.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cell Biology
Adriana Limone, Iolanda Veneruso, Antonella Izzo, Maurizio Renna, Raffaella Bonavita, Silvia Piscitelli, Gaetano Cali, Sergio De Nicola, Patrizia Riccio, Valeria D'Argenio, Antonio Lavecchia, Daniela Sarnataro
Summary: Currently, the therapeutic strategies for neurodegenerative diseases are either ineffective or at early preclinical stages. However, a study has found that NSC48478, a 37/67kDa laminin receptor inhibitor, can induce the conversion of LC3-I to LC3-II and promote autophagy in mouse neuronal cells. This compound mainly activates the non-canonical m-TOR-independent endocytic pathway involving Rab proteins, and upregulates genes related to endocytosis, vesicle fusion and autolysosomal maturation. These findings suggest that NSC48478 could be a useful tool for further studies in pathological conditions.
Article
Biochemistry & Molecular Biology
Carmen Cerchia, Emanuela Roscetto, Rosarita Nasso, Maria Rosaria Catania, Emmanuele De Vendittis, Antonio Lavecchia, Mariorosario Masullo, Rosario Rullo
Summary: In this study, a virtual screening method was used to discover a novel inhibitor of the microaerophile Streptococcus mutans' superoxide dismutase (SmSOD), which is responsible for dental plaque formation. The compound ALS-31 was found to inhibit SmSOD and other SODs, affecting their catalytic activity. In addition, ALS-31 was shown to inhibit planktonic growth and biofilm formation of S. mutans cultures. A derivative of ALS-31, ALS-31-9, exhibited improved inhibition power. This research provides insights for future drug design studies to combat dental caries.
Article
Immunology
Seyed Mohammad Lellahi, Waqas Azeem, Yaping Hua, Benjamin Gabriel, Kristin Paulsen Rye, Hakon Reikvam, Karl-Henning Kalland
Summary: Conventional type 1 dendritic cells (cDC1) and conventional type 2 dendritic cells (cDC2) are being considered as alternative options to monocyte-derived dendritic cells (moDCs) in cancer immunotherapy. However, the low numbers of cDCs in peripheral blood and their extensive spontaneous apoptosis and death in culture within 24hrs pose challenges. The study found that GM-CSF improved the viability of both cDC1 and cDC2, while Flt3-L and IL-4 specifically increased the viability of cDC1 and cDC2, respectively. Combinations of these three cytokines further improved the viability of both cDCs at different time points.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Knut Anders Mosevoll, Bent Are Hansen, Ingunn Margareetta Gundersen, Hakon Reikvam, Oyvind Bruserud, Oystein Bruserud, Oystein Wendelbo
Summary: This study investigated the serum metabolomic profile of patients with bacterial sepsis at hospital admission. The results showed significant differences in metabolites between Sepsis-3 and Sepsis-2/SIRS patients, indicating distinct metabolic characteristics at the time of hospitalization. Additionally, some Sepsis-3 patients had metabolic profiles similar to Sepsis-2/SIRS patients, even with a high total SOFA score. Overall, the metabolic profile of patients with bacterial sepsis at hospital admission is heterogeneous.
Editorial Material
Biochemistry & Molecular Biology
Carmen Cerchia, Antonio Lavecchia
Article
Hematology
Hakon Reikvam
Summary: This article discusses the significance of FLT3 mutations and various aspects of this mutation in light of new understanding and research progress. The improvement in therapeutic approaches for FLT3 mutated AML, including the introduction of FLT3 inhibitors and measurable residual disease monitoring, is also emphasized. The treatment of FLT3 mutated AML is still in need of further research.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Review
Cell Biology
Oystein Bruserud, Knut Anders Mosevoll, Oyvind Bruserud, Hakon Reikvam, Oystein Wendelbo
Summary: Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, resulting in organ dysfunction. Neutrophils play a crucial role in the innate immune response and regulation of the host immune system. The regulation of neutrophil migration is crucial in both the host response to infection and the development of organ dysfunction in sepsis.
Article
Biochemistry & Molecular Biology
Rosario Rullo, Carmen Cerchia, Rosarita Nasso, Virgilio Romanelli, Emmanuele De Vendittis, Mariorosario Masullo, Antonio Lavecchia
Summary: Xanthine oxidase (XO) is a flavoprotein that plays a crucial role in the oxidation of hypoxanthine to uric acid. Abnormal functions of XO can lead to severe diseases, such as gout-causing hyperuricemia and tissue damage. In this study, we identified four non-purine-like compounds (ALS-1, -8, -15, and -28) that directly inhibit XO activity. Among them, ALS-28 showed the highest potency as an inhibitor. These structurally unrelated compounds have the potential to be further developed into lead compounds.
Review
Medicine, General & Internal
Trym Fauchald, Bjorn Blomberg, Hakon Reikvam
Summary: This study reviewed reported cases of tuberculosis-associated hemophagocytic lymphohistiocytosis (HLH) in the English literature and summarized the epidemiology, diagnostics, treatment, and mortality in these cases. Among 116 patients with tuberculosis-associated HLH, there was a male:female ratio of about 3:2 and the age at presentation ranged from 12 days to 83 years. Most patients received both tuberculostatic and specific immunomodulating treatment, resulting in a higher survival rate compared to those receiving only one type of treatment. The overlapping symptoms between disseminated tuberculosis and HLH pose challenges in diagnosis and treatment, leading to increased mortality. Therefore, tuberculosis should be considered as a potential trigger of HLH, and appropriate investigations are needed for diagnosis and treatment.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Sushma Bartaula-Brevik, Calum Leitch, Maria Hernandez-Valladares, Elise Aasebo, Frode S. Berven, Frode Selheim, Annette K. Brenner, Kristin Paulsen Rye, Marie Hagen, Hakon Reikvam, Emmet Mccormack, Oystein Bruserud, Tor Henrik Anderson Tvedt
Summary: V-ATPase inhibitors have dose-dependent antiproliferative and proapoptotic effects on primary AML cells, but the effects vary among patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Oncology
Oystein Bruserud, Hakon Reikvam
Summary: Acute myeloid leukemia (AML) is a blood cancer disease that requires intensive anticancer treatment and stem cell transplantation. Inhibiting the protein kinase CK2 shows promise as a strategy for treating AML, both as monotherapy and in combination with other drugs. CK2 plays a vital role in signaling pathways in AML cells, and high CK2 levels are associated with decreased survival. Further research is needed to investigate the potential benefits of CK2 inhibition in AML treatment.
Review
Biology
Andrea Solberg, Hakon Reikvam
Summary: Iron is essential for muscle function and oxygen transport in the body. Adequate iron levels are necessary for athletes, as deficiency can reduce physical performance. This review examines the importance of iron values, markers, and factors that can affect iron metabolism for physical performance.
Article
Oncology
Lise Mayrin Okland Thunestvedt, Lars Helgeland, Ingeborg Margrethe Bachmann, Asa Karlsdottir, Torjan Magne Haslerud, Hakon Reikvam
Summary: Basal cell carcinoma (BCC) is a common cancer in Caucasians, but rarely metastasizes. This case report presents a patient with primary BCC in the sub-mammary area, which metastasized to the skeleton and bone marrow. Surgery was performed successfully, but the patient developed anemia and inflammation markers post-surgery. [F-18]FDG PET/CT showed extensive uptake, and biopsy confirmed BCC infiltration.
Article
Health Care Sciences & Services
Henriette K. Helland, Thorkild Tylleskaer, Monika Kvernenes, Hakon Reikvam
Summary: This study investigated the impact of the transition to digital education on medical students at the University of Bergen. It focused on students' motivation, experience of learning outcomes, and fear of missing out on important learning. The findings showed that students were generally unhappy with the quality of teaching, particularly in clinical skills.