Review
Biochemistry & Molecular Biology
Pawel Lukasik, Irena Baranowska-Bosiacka, Katarzyna Kulczycka, Izabela Gutowska
Summary: Recent studies have shown that small molecule drugs targeting CDK inhibitors have become attractive options for treating cancer and neurodegenerative disorders. Most CDK inhibitors target the ATP binding pocket, but the similarity in structure among CDK kinases makes achieving selectivity challenging. Therefore, inhibitors binding outside the ATP binding site have attracted great interest for their potential applications in the biomedical field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Johannes Tobias Thiel, Adrien Daigeler, Jonas Kolbenschlag, Katarzyna Rachunek, Sebastian Hoffmann
Summary: Soft tissue sarcomas (STSs) are rare malignant conditions that are difficult to treat. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. This review discusses the role of CDK signaling in STS development and its implications for targeted treatment.
Review
Pharmacology & Pharmacy
Zhiyi Zhang, Jie Song, Cao Xie, Jun Pan, Weiyue Lu, Min Liu
Summary: Pancreatic cancer is a highly malignant tumor that is difficult to diagnose early, with most patients diagnosed in advanced stages. Current main treatments include chemotherapy, which has not significantly improved patient prognosis.
Article
Chemistry, Multidisciplinary
Lavleen Mader, John J. Hayward, Lisa A. Porter, John F. Trant
Summary: This study reports an improved and refocused synthesis method for CDK2 inhibitors, allowing for effective exploration of substituents at the O-6 position.
NEW JOURNAL OF CHEMISTRY
(2022)
Review
Oncology
Mengna Zhang, Lingxian Zhang, Ruoxuan Hei, Xiao Li, Haonan Cai, Xuan Wu, Qiping Zheng, Cheguo Cai
Summary: Dysregulated cell division is a key feature of cancer, and blocking cell division through CDK inhibitors (CDKIs) shows potential for cancer treatment. CDK4/6 inhibitors have been approved for metastatic breast cancer, but first-generation pan-CDK inhibitors have not been widely approved due to non-selectivity and toxicity. Efforts are being made to enable pan-CDK inhibitors for clinical application and combination therapy strategies have been developed to reduce toxicity and side effects.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Dermatology
L. Steele, H. L. Lee, T. Maruthappu, E. A. O'Toole
Summary: Recent meta-analyses on Janus kinase (JAK) inhibitors in alopecia areata (AA) may be biased due to exclusion of trial registries. A study assessing JAK inhibitor trials in AA found that topical JAK inhibitors have a higher termination rate and may be less effective than oral JAK inhibitors.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2021)
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)
Review
Biochemistry & Molecular Biology
Dariusz Rozkiewicz, Justyna Magdalena Hermanowicz, Iwona Kwiatkowska, Anna Krupa, Dariusz Pawlak
Summary: There has been increasing interest in Bruton's tyrosine kinase (BTK) and its inhibitors in recent decades. BTK is a mediator of the B-cell receptor signaling pathway and has an impact on B-cell proliferation and differentiation. Studies have shown that BTK inhibitors, such as ibrutinib, have potential in treating various cancers and autoimmune diseases. This review article summarizes the latest findings on BTK and its inhibitors, focusing on their clinical applications in cancer and chronic inflammatory diseases.
Review
Chemistry, Medicinal
Austin Lui, Jordan Vanleuven, David Perekopskiy, Dewey Liu, Desiree Xu, Omar Alzayat, Taiseer Elgokhy, Timothy Do, Meghan Gann, Ryan Martin, Da-Zhi Liu
Summary: Cancer and neurological disorders share a common mechanism of aberrant cell cycle re-entry, suggesting that some cancer therapies may be applicable for neurological treatments. However, there is still a lack of FDA-approved drugs for neurological disorders.
Review
Biochemistry & Molecular Biology
Ni Made Pitri Susanti, Daryono Hadi Tjahjono
Summary: The cell cycle is crucial in cell development, and its progression is controlled by endogenous CDK inhibitors, CDKs, and cyclins. Dysregulation of the cell cycle can lead to cancer, making CDK a natural target for anticancer therapy. Understanding CDK structures and complexes with drugs helps in developing CDK inhibitors, from non-selective to selective CDK4/CDK6 inhibitors applied in clinical cancer treatment.
Review
Oncology
Yi Zhang, Zhuo Ma, Ximu Sun, Xin Feng, Zhuoling An
Summary: CDK4/6 inhibitors increase the risk of ILD/pneumonitis in cancer patients. Awareness of these rare adverse events should be enhanced.
Article
Biochemistry & Molecular Biology
Andrea Rizzuto, Angelo Pirrera, Emilia Gigliotta, Salvatrice Mancuso, Candida Vullo, Giulia Maria Camarda, Cristina Rotolo, Arianna Roppolo, Corinne Spoto, Massimo Gentile, Cirino Botta, Sergio Siragusa
Summary: The current treatment for chronic lymphocytic leukemia (CLL) relies on chemotherapy, immunotherapy, and targeted inhibitors. However, the multitude of choices and lack of direct comparisons make treatment selection challenging. To address this, a systematic review and meta-analysis of clinical trials in CLL were performed. The results showed that a combination of obinutuzumab with acalabrutinib was the most effective treatment, especially in the absence of del17/P53 mutations. Additionally, chemotherapy is becoming less relevant in the first-line treatment of CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Shirley V. Wang, Sebastian Schneeweiss, RCT-DUPLICATE Initiative
Summary: Nonrandomized studies using insurance claims databases can provide real-world evidence on the effectiveness of medical products. By emulating the design parameters of randomized clinical trials and quantifying the agreement between database studies and RCTs, this study highlights the importance of closely replicating trial design and measurements for reliable conclusions.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Review
Chemistry, Medicinal
Deendyal Bhurta, Sandip B. Bharate
Summary: This article critically analyzed the chemical diversity of CDK inhibitors, with amino-pyrimidine being the most represented scaffold. The discussion included selectivity aspects among CDKs, dose-limiting toxicities in clinical trials, and the most advanced clinical candidates. The article also touched on the changing paradigm towards selective inhibitors and provided an overview of ATP-binding pockets of all druggable CDKs.
MEDICINAL RESEARCH REVIEWS
(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
Environmental Sciences
Stefano Palazzolo, Isabella Caligiuri, Andrea Augusto Sfriso, Matteo Mauceri, Rossella Rotondo, Davide Campagnol, Vincenzo Canzonieri, Flavio Rizzolio
Summary: This study compares the effects of long-chain and short-chain PFAS on mouse liver organoids, revealing the impact of these compounds on organoid morphology and enzyme activity. Long-chain PFAS exhibit higher toxicity, while short-chain PFAS only have a limited effect on organoid morphology. The study also shows that organoid testing could serve as a fast and reproducible platform for assessing the toxicity of pollutants.
Correction
Biochemistry & Molecular Biology
Pietro Mancuso, Rossella Tricarico, Vikram Bhattacharjee, Laura Cosentino, Yuwaraj Kadariya, Jaroslav Jelinek, Emmanuelle Nicolas, Margret Einarson, Neil Beeharry, Karthik Devarajan, Richard A. Katz, Dorjbal G. Dorjsuren, Hongmao Sun, Anton Simeonov, Antonio Giordano, Joseph R. Testa, Guillaume Davidson, Irwin Davidson, Lionel Larue, Robert W. Sobol, Timothy J. Yen, Alfonso Bellacosa
Review
Cell Biology
Pierluigi Scalia, Stephen J. Williams, Yoko Fujita-Yamaguchi, Antonio Giordano
Summary: The IGFs are important growth factors that play a key role in cell growth and cell cycle progression through their cellular receptors. Understanding the intracellular signaling mechanisms of IGFs is crucial for cancer research. This study provides a comprehensive summary of the current understanding of the regulatory mechanisms of IGFs in cancer and suggests new perspectives for further research.
Article
Anatomy & Morphology
Ilenia Severi, Silvia Abbatelli, Jessica Perugini, Eleonora Di Mercurio, Martina Senzacqua, Antonio Giordano
Summary: This study is the first comprehensive morphological investigation into the distribution and physiological role of BChE in the mouse gastrointestinal tract. BChE-positive cells were found in various digestive organs, such as the stomach, liver, and intestine, and were closely linked to ghrelin production.
JOURNAL OF ANATOMY
(2023)
Article
Dermatology
Francesco De Logu, Roberto Maglie, Mustafa Titiz, Giulio Poli, Lorenzo Landini, Matilde Marini, Daniel Souza Monteiro de Araujo, Gaetano De Siena, Marco Montini, Daniela Almeida Cabrini, Michel Fleith Otuki, Priscila Lucia Pawloski, Emiliano Antiga, Tiziano Tuccinardi, Joao Batista Calixto, Pierangelo Geppetti, Romina Nassini, Eunice Andre
Summary: The study reveals that the genetic deletion or pharmacological antagonism of TRPV4 can attenuate itch in a mouse model of psoriasis. Human psoriatic lesions express multiple microRNAs, including miR-203b-3p, which can induce itch in mice through the activation of 5-HTR2B and TRPV4. Computer simulation shows that the core sequence of miR-203b-3p (GUUAAGAA) targets the extracellular side of 5-HTR2B.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biology
Francesco Balestri, Giulio Poli, Lucia Piazza, Mario Cappiello, Roberta Moschini, Giovanni Signore, Tiziano Tuccinardi, Umberto Mura, Antonella Del Corso
Summary: The increased glucose levels in diabetes lead to metabolic alterations and the onset of diabetic complications. Blocking the polyol pathway through aldose reductase inhibition is considered a valuable strategy. However, the enzyme also has a beneficial effect in cells, so the use of differential inhibitors has been proposed to preserve its detoxifying action. This study analyzed derivatives of catechins as potential differential inhibitors of aldose reductase and found promising inhibitory effects.
Review
Biochemistry & Molecular Biology
Giovanni Ciccarelli, Stefano Conte, Giovanni Cimmino, Patrizia Maiorano, Andrea Morrione, Antonio Giordano
Summary: Atherosclerosis is a complex disease involving metabolic processes and inflammation. Despite improved therapies, a significant residual risk remains due to unmet therapeutic targets. Endothelial dysfunction and lipid infiltration are primary causes of atherosclerotic plaque progression. Mitochondrial dysfunction can affect arterial wall cells, leading to oxidative stress, chronic inflammation, and intracellular lipid deposition. Evaluating mitochondrial defects through the detection and characterization of mitochondrial DNA (mtDNA) is crucial, and mitochondria-targeting therapies show promise in treating atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giulio Poli, Gian Carlo Demontis, Andrea Sodi, Alessandro Saba, Stanislao Rizzo, Marco Macchia, Tiziano Tuccinardi
Summary: A combined strategy of molecular dynamics simulations and bioinformatics was used to evaluate the pathogenicity of hRPE65 missense mutations. The results may support the reclassification of VUS and assist clinicians in determining the eligibility for gene therapy of patients with such variants.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sedigheh Cheraghali, Ghasem Dini, Isabella Caligiuri, Michele Back, Flavio Rizzolio
Summary: In this study, hierarchical MnZn ferrite nanoparticles were synthesized and their surface characteristics were improved by PEGylation. In vitro MRI studies confirmed the ability of the synthesized nanoparticles as a contrast agent. Results were compared with normal structured MnZn ferrite nanoparticles.
Review
Oncology
Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. V. Iozzo, Antonio Giordano, Andrea Morrione
Summary: Progranulin plays an important pro-tumorigenic role in various solid tumors and has diagnostic and prognostic values in multiple tumor types. The molecular mechanisms underlying progranulin's function in cancer are not fully understood, but recent evidence suggests a strong context-dependency of progranulin signaling. This review focuses on summarizing the current evidence supporting the pro-oncogenic role of progranulin and its molecular mechanisms of action in cancer.
Review
Pharmacology & Pharmacy
Tanja Jesenko, Simona Kranjc Brezar, Maja Cemazar, Alice Biasin, Domenico Tierno, Bruna Scaggiante, Mario Grassi, Chiara Grassi, Barbara Dapas, Nhung Hai Truong, Michela Abrami, Fabrizio Zanconati, Deborah Bonazza, Flavio Rizzolio, Salvatore Parisi, Giorgia Pastorin, Gabriele Grassi
Summary: Hepatocellular carcinoma (HCC) is a major global health challenge, ranking third in cancer deaths worldwide. Despite recent therapeutic advances, prognosis remains poor, necessitating the development of novel strategies. This study focuses on targeting molecules with aberrant expression confined to tumor cells, particularly non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs. These ncRNAs play a significant role in regulating various aspects of HCC, including proliferation, apoptosis, invasion, and metastasis. The review provides the latest state-of-the-art approaches, highlighting key trends and opportunities for advanced and efficacious HCC treatments.
Review
Agriculture, Dairy & Animal Science
Giovanna Liguori, Anna Costagliola, Renato Lombardi, Orlando Paciello, Antonio Giordano
Summary: Animal-assisted interventions (AAIs) are planned activities carried out in multidisciplinary teams with educational, therapeutic, and recreational purposes. These interventions offer many advantages to subjects but may expose them to zoonotic-pathogen transmission. Therefore, ensuring positive animal welfare and implementing preventive measures are crucial for the safety of patients.
Article
Chemistry, Medicinal
Miriana Di Stefano, Salvatore Galati, Lisa Piazza, Carlotta Granchi, Simone Mancini, Filippo Fratini, Marco Macchia, Giulio Poli, Tiziano Tuccinardi
Summary: The application of artificial intelligence and machine learning methods is increasingly popular in computational toxicology and drug design. VenomPred 2.0 is the new and improved version of a free web tool for toxicological predictions, offering a powerful platform for multifaceted and human-interpretable in silico toxicity profiling of chemicals.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Biochemistry & Molecular Biology
Alfredo Caturano, Margherita D'Angelo, Andrea Mormone, Vincenzo Russo, Maria Pina Mollica, Teresa Salvatore, Raffaele Galiero, Luca Rinaldi, Erica Vetrano, Raffaele Marfella, Marcellino Monda, Antonio Giordano, Ferdinando Carlo Sasso
Summary: Oxidative stress plays a critical role in the development and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defense mechanisms leads to cellular damage and dysfunction. By understanding and addressing oxidative stress, it may be possible to alleviate the burden of diabetes and improve patient outcomes.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Materials Science, Biomaterials
Kanwal Asif, Muhammad Adeel, Md. Mahbubur Rahman, Isabella Caligiuri, Tiziana Perin, Maja Cemazar, Vincenzo Canzonieri, Flavio Rizzolio
Summary: ChemoDynamic Therapy (CDT) utilizes Fenton/Fenton-like reactions to generate oxidative stress for cancer treatment. However, the limited catalyst ions and ROS scavenging activity of GPX4 restrict its application. Therefore, an efficient strategy to regulate the Fenton reaction (using dual metal cations) and inhibit GPX4 activity is highly desired.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
