Drug Discovery Today最新文献

Photodynamic therapy (PDT) is a minimally invasive treatment showing promise against cancer and microbial infections. PDT targets tumor cells while sparing healthy tissue, reducing side effects. It induces immunogenic cell death, potentially stimulating antitumor immune responses and reducing cancer recurrence. In microbial treatment, PDT effectively combats bacteria, fungi and viruses. Combining PDT with chemotherapy, radiotherapy and immunotherapy enhances its efficacy. However, challenges such as tumor hypoxia, limited tissue penetration and phototoxicity necessitate ongoing research efforts to optimize PDT protocols and overcome limitations. Overall, PDT is versatile and continually advancing with refined protocols to improve its clinical utility against cancer and microbial infections.

Scaffold hopping is a design approach involving alterations to the core structure of an already bioactive scaffold to generate novel molecules to discover bioactive hit compounds with innovative core structures. Scaffold hopping enhances selectivity and potency while maintaining physicochemical, pharmacodynamic (PD), and pharmacokinetic (PK) properties, including toxicity parameters. Numerous molecules have been designed based on a scaffold-hopping strategy that showed potent inhibition activity against multiple targets for the diverse types of malignancy. In this review, we critically discuss recent applications of scaffold hopping along with essential components of medicinal chemistry, such as structure–activity relationship (SAR) profiles. Moreover, we shed light on the limitations and challenges associated with scaffold hopping-based anticancer drug discovery.

Celiac disease (CeD), an autoimmune disorder triggered by gluten, affects around 1% of the global population. Standard treatment is a strict gluten-free diet (GFD), which poses significant challenges due to dietary restrictions, cross-contamination and subsequent persistent intestinal inflammation. This underscores the need for new treatment options addressing the complex pathophysiology of CeD. Recent research focuses on developing drugs that target intestinal barrier regeneration, gluten peptide modification, immune response alteration, and gut microbial ecosystem modulation. These approaches offer potential for more effective management of CeD beyond GFD. Gluten-independent treatments may be particularly relevant under the FDA’s draft guidance for CeD, which emphasizes drug development as an adjunct to GFD for patients with ongoing signs and symptoms of CeD despite strict GFD.

Three-dimensional (3D) cell culture techniques, which are superior to 2D methods in viability and functionality, are being used to develop innovative cancer vaccines. Tumor spheroids, which are structurally and functionally similar to actual tumors, can be developed using 3D cell culture. These spheroid vaccines have shown superior antitumor immune responses to 2D cell-based vaccines. Dendritic cell vaccines can also be produced more efficiently using 3D cell culture. Personalized cancer vaccines are being developed using 3D cell culture, providing substantial benefits over 2D methods. The more natural conditions of 3D cell culture might promote the expression of tumor antigens not expressed in 2D culture, potentially allowing for more targeted vaccines by co-culturing tumor cells with other cell types. Advanced cancer vaccines using 3D cell cultures are expected soon.

The pharmaceutical industry is undergoing a sweeping transformation, driven by technological innovations, demographic shifts, regulatory changes and consumer expectations. For adaptive players in pharma to excel in this rapidly changing landscape, which will be markedly different from today by 2030 and beyond, they will require a different set of skills, capabilities and mindsets, as well as a willingness to collaborate and co-create value with multiple stakeholders. The industry needs to rewrite the textbook for pharma by embracing and implementing four key dimensions of change: digitalization, personalization, collaboration and innovation. In this article, we will examine how these dimensions of change are reshaping the industry, and provide practical and strategic guidance based on best practices and examples. Specifically, adaptive pharma companies should embrace the use of advanced digital technologies, such as artificial intelligence and machine learning, to streamline processes and solve challenges rapidly. Personalization, both in medicine and patient engagement, will also be key to success in the ‘digital revolution’, and a collaborative approach involving partnerships with tech start-ups, health-care providers and regulatory bodies will also be essential to create an integrated and responsive health-care ecosystem. Using these ideas for a rewritten textbook for pharma, adaptive players in pharma will evolve to be personalized and digitized health-focused organizations that provide comprehensive solutions which go beyond drugs and devices.

The utilization of ionic liquids (ILs) in pharmaceutical drug delivery applications has seen significant expansion in recent years, owing to their distinctive characteristics and inherent adjustability. These innovative compounds can be used to tackle challenges associated with traditional dosage forms, such as polymorphism, inadequate solubility, permeability, and efficacy in topical drug delivery systems. Here, we provide a brief classification of ILs, and their effectiveness in augmenting transmucosal drug delivery approaches by improving the solubility and permeability of active pharmaceutical ingredients (APIs) by temporary mucus modulation aiding the paracellular transport of APIs, prolonging drug retention, and, thus, aiding controlled drug release across various mucosal surfaces. We also highlight potential advances in, and future perspectives of, IL-based formulations in mucosal drug delivery.

This perspective paper explores the synergistic potential of blockchain and artificial intelligence (AI) in transforming healthcare. It begins with an overview of blockchain’s role in healthcare data management, security, the pharmaceutical supply chain, clinical trials, and health insurance. The discussion then shifts to the impact of AI on healthcare, followed by an examination of integrated AI–blockchain platforms and their benefits. Technical challenges, limitations, and solutions related to these technologies are scrutinized. The paper addresses regulatory compliance and ethical considerations, and proposes future directions for their implementation. It concludes with research and implementation guidelines, offering a roadmap for harnessing blockchain and AI to enhance healthcare outcomes.

Digital therapeutics (DTx) is a recently conceived idea in health care that aims to cure ailments and modify patient behavior by employing a range of digital technologies. Notably, when traditional medication is not entirely efficacious, DTx offers an innovative avenue for treatments linked to dysfunctional behaviors and lifestyle management. DTx involves extremely adaptable therapeutic devices that empower greater patient engagement in treating illness, using algorithms to collect, transfer and analyze the patient’s data. Efficient clinical monitoring and supervision at the individual level by remote access and algorithms for a range of diseases is made possible by integrating machine learning and artificial intelligence with DTx. There is a potentially large worldwide market for DTx owing to its convenient, personalized therapies.

The primary challenge in TB treatment is the emergence of multidrug-resistant TB (MDR-TB). One of the major factors responsible for MDR is the upregulation of efflux pumps. Permeation-glycoprotein (P-gp), an efflux pump, hinders the bioavailability of the administered drugs inside the infected cells. Simultaneously, angiogenesis, the formation of new blood vessels, contributes to drug delivery complexities. TB infection triggers a cascade of events that upregulates the expression of angiogenic factors and P-gp. The combined action of P-gp and angiogenesis foster the emergence of MDR-TB. Understanding these mechanisms is pivotal for developing targeted interventions to overcome MDR in TB. P-gp inhibitors, such as verapamil, and anti-angiogenic drugs, including bevacizumab, have shown improvement in TB drug delivery to granuloma. In this review, we discuss the potential of P-gp inhibitors as an adjunct therapy to shorten TB treatment.

This review explores the potential antiviral properties of various plant-based compounds, including polyphenols, phytochemicals, and terpenoids. It emphasizes the diverse functionalities of compounds such as epigallocatechin‐3‐gallate (EGCG), quercetin, griffithsin (GRFT,) resveratrol, linalool, and carvacrol in the context of respiratory virus infections, including SARS-CoV-2. Emphasizing their effectiveness in modulating immune responses, disrupting viral envelopes, and influencing cellular signaling pathways, the review underlines the imperative for thorough research to establish safety and efficacy. Additionally, the review underscores the necessity of well-designed clinical trials to evaluate the efficacy and safety of these compounds as potential antiviral agents. This approach would establish a robust framework for future drug development efforts focused on bolstering host defense mechanisms against human respiratory viral infections.