Drug Discovery Today最新文献

Neurodegenerative diseases are challenging to cure. To date, no cure has been found for Alzheimer’s disease or Parkinson’s disease, and current treatments are able only to slow the progression of the diseases and manage their symptoms. After an introduction to the complex biology of these diseases, we discuss the beneficial effect of selenium-containing agents, which show neuroprotective effects in vitro or in vivo. Indeed, selenium is an essential trace element that is being incorporated into innovative organoselenium compounds, which can improve outcomes in rodent or even primate models with neurological deficits. Herein, we critically discuss recent findings in the field of selenium-based applications in neurological disorders.

The application of nanotechnology has significantly advanced the development of novel platforms that enhance disease treatment and diagnosis. A key innovation in this field is the creation of antitoxin nanoparticles (ATNs), designed to address toxin exposure. These precision-engineered nanosystems have unique physicochemical properties and selective binding capabilities, allowing them to effectively capture and neutralize toxins from various biological, chemical, and environmental sources. In this review, we thoroughly examine their therapeutic and diagnostic potential for managing toxin-related challenges. We also explore recent advancements and offer critical insights into the design and clinical implementation of ATNs.

Metal-based drugs hold promise as potent anticancer agents owing to their unique interactions with cellular targets. This review discusses recent advances in our understanding of the intricate molecular interactions of metal-based anticancer compounds with specific therapeutic targets in cancer cells. Advanced computational and experimental methodologies delineate the binding mechanisms, structural dynamics and functional outcomes of these interactions. In addition, the review sheds light on the precise modes of action of these drugs, their efficacy and the potential avenues for further optimization in cancer-treatment strategies and the development of targeted and effective metal-based therapies for combating various forms of cancer.

Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively. However, despite the US FDA approving over 100 small-molecule targeted antitumor drugs, challenges such as low response rates and drug resistance persist. This review delves into the possibility of using small molecules to treat persistent or spreading PC, highlighting the challenges and the urgent need for a diverse selection of inhibitors to develop more effective treatment strategies.

As a global health challenge, cancer prompts continuous exploration for innovative therapies that are also based on new targets. One promising avenue is targeting the shelterin protein complex, a safeguard for telomeres crucial in preventing DNA damage. The role of shelterin in modulating ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) kinases, key players in the DNA damage response (DDR), establishes its significance in cancer cells. Disrupting these defence mechanisms of shelterins, especially in cancer cells, renders telomeres vulnerable, potentially leading to genomic instability and hindering cancer cell survival. In this review, we outline recent approaches exploring shelterins as potential anticancer targets, highlighting the prospect of developing selective molecules to exploit telomere vulnerabilities toward new innovative cancer treatments.

Antibody–drug conjugates (ADCs), from prototypes in the 1980s to first- and second-generation products in the 2000s, and now in their multiformats, have progressed tremendously to meet oncological challenges. Currently, 13 ADCs have been approved for medical practice, with over 200 candidates in clinical trials. Moreover, ADCs have evolved into different formats, including bispecific ADCs, probody–drug conjugates, pH-responsive ADCs, target-degrading ADCs, and immunostimulating ADCs. Technologies from biopharmaceutical industries have a crucial role in the clinical transition of these novel biotherapeutics. In this review, we highlight several features contributing to the prosperity of bioindustrial ADC development. Various proprietary technologies from biopharmaceutical companies are discussed. Such advances in biopharmaceutical industries are the backbone for the success of ADCs in development and clinical application.

Vascular tone is a major element in the control of hemodynamics. Transient receptor potential (TRP) channels conducting monovalent and/or divalent cations (e.g. Na⁺ and Ca²⁺) are expressed in the vasculature. Accumulating evidence suggests that TRP channels participate in regulating vascular tone by regulating intracellular Ca²⁺ signaling in both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Aberrant expression/function of TRP channels in the vasculature is associated with vascular dysfunction in systemic/pulmonary hypertension and metabolic syndromes. This review intends to summarize our current knowledge of TRP-mediated regulation of vascular tone in both physiological and pathophysiological conditions and to discuss potential therapeutic approaches to tackle abnormal vascular tone due to TRP dysfunction.

Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising. Bacteriophages and their gene products have garnered interest as potential therapeutic options for bacterial infections. Here, we have compiled information on bacteriophages and their products that can kill Mycobacterium tuberculosis or NTM. We summarize the mechanisms whereby viable phages can access macrophage-resident bacteria and not elicit immune responses, review methodologies of pharmaceutical product development containing mycobacteriophages and their gene products, mainly lysins, in the context of drug regulatory requirements and we discuss industrially relevant methods for producing pharmaceutical products comprising mycobacteriophages, emphasizing delivery of mycobacteriophages to the lungs. We conclude with an outline of some recent case studies on mycobacteriophage therapy.