Drug Discovery Today最新文献

microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.

The ability to selectively target cancer cells makes antibody–drug conjugates (ADCs) promising therapeutic options. They have been tested in clinical trials as a vehicle for tumor-specific delivery of cytotoxic payloads for a range of cancers. However, systemic administration of oncolytic virotherapy is challenging, because only a small portion of injected viruses reach the target. Despite the approval of higher viral doses, most viruses still end up in the liver, potentially causing toxicity in that organ. Integrating ADCs with virotherapy in the form of antibody–virus conjugates or virus–drug conjugates can potentially overcome these challenges and improve therapeutic outcomes.

Tuberculosis (TB) is a world health challenge the treatment of which is impacted by the rise of drug-resistant strains. Thus, there is an urgent need for new antitubercular compounds and novel approaches to improve current TB therapy. The zebrafish animal model has become increasingly relevant as an experimental system. It has proven particularly useful during early development for aiding TB drug discovery, supporting both the discovery of new insights into mycobacterial pathogenesis and the evaluation of therapeutical toxicity and efficacy in vivo. In this review, we summarize the past two decades of zebrafish–Mycobacterium marinum research and discuss its contribution to the field of bioactive antituberculosis therapy development.

Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)–Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.

A global biopharma company, GSK, and the University of Strathclyde have developed an expansive and transformative research and training partnership originating in chemistry-aligned disciplines, with subsequent extensive expansion across further areas of the company. This has opened unique approaches for the delivery of collaborative research innovations while also enhancing the professional development and learning of GSK personnel, in addition to other embedded researchers and collaborating scientists, on a pathway towards more rapid and efficient discovery of new medicines.