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Recent Insights in Multi-Target Drugs in Pharmacology and Medicinal Chemistry.

Many of the drugs used in treatment today have been designed based on the "specificity paradigm". Resistance has developed against drugs designed using this approach, leading to a decrease in their effectiveness. In addition, it is well-documented in the literature that diseases with complex etiologies, such as Alzheimer's, Parkinson's, and cancer are influenced by multiple genetic and/or environmental factors. As a result, specificity paradigm is often insufficient for treating these diseases. Therefore, there is a need to develop drugs that interact with multiple targets simultaneously throu

Тонаберсат усиливает цитотоксичность в глиобластоме с помощью темозоломида путем нарушения межклеточной связи через коннексин 43 ингибирование.

Клетки глиобластомы зависят от коннексина 43 (Cx43) на основе данных о разрыве (GJs) для межклеточной связи, позволяющей им интегрироваться в широко разветвленную злокачественную сеть. Несмотря на многообещающие перспективы новой целевой терапии, отсутствие клинически осуществимых ингибиторов GJ препятствует их внедрению в клинической практике. В настоящем исследовании мы изучили тонаберсат (ТО) — лекарство, вызывающее кровоизлияние в мозг и имеющее свойства GJ-ингиберия, с точки зрения его способности разобрать межклеточную связь в сетях глиобластомы. Для изучения функциональной межклеточной

Ferroptosis and its emerging role in esophageal cancer.

The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

Quantification of promoting efficiency and reducing toxicity of Traditional Chinese Medicine: A case study of the combination of Tripterygium wilfordii hook. f. and Lysimachia christinae hance in the treatment of lung cancer.

Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is stil

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.

Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can c

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… Phenyl-1H-1,2,3-triazole analog 47 Coumarins, also known as benzopyrans, are versatile compounds found naturally in plants and have been used in herbal remedies for a long time. …

The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to

Genus Sophora: a comprehensive review on secondary chemical metabolites and their biological aspects from past achievements to future perspectives.

Sophora is deemed as one of the most remarkable genera of Fabaceae, and the third largest family of flowering plants. The genus Sophora comprises approximately 52 species, 19 varieties, and 7 forms that are widely distributed in Asia and mildly in Africa. Sophora species are recognized to be substantial sources of broad spectrum biopertinent secondary metabolites namely flavonoids, isoflavonoids, chalcones, chromones, pterocarpans, coumarins, benzofuran derivatives, sterols, saponins (mainly triterpene glycosides), oligostilbenes, and mainly alkaloids. Meanwhile, extracts and isolated compoun

The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine parac