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Traditional cell-based disease models often fail to adequately represent key disease characteristics, increasing the risk of subsequent attrition in clinical trials. This article presents a set of principles for disease-relevant assays, and discusses new opportunities for exploiting advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells as well as 3D co-culture and organ-on-a-chip systems, which are being complemented by progress with single-cell imaging and gene editing technologies.
Non-coding RNAs (ncRNAs) may affect normal gene expression and disease progression, thereby representing potential drug targets. Here, Matsui and Corey assess the potential and challenges in therapeutically exploiting ncRNA species — including microRNA, intronic RNA, repetitive RNA and long ncRNA — highlighting key lessons learned during the development of technologies targeting mRNA.
This article discusses evolving preclinical strategies for detecting drug-induced cardiotoxicity using human ion-channel assays, human-basedin silicoreconstructions and human stem cell-derived cardiomyocytes. Such strategies have the potential to improve the early detection of genuine cardiotoxicity risks, reducing the likelihood of mistakenly discarding viable drug candidates and speeding worthy drugs into clinical trials.
Members of the integrin family of receptors, which are involved in cell–cell adhesion, have been successfully targeted for cardiovascular disease, multiple sclerosis and inflammatory bowel disease. Ley and colleagues review the biological basis for the development of the next generation of integrin-targeted drugs, highlighting lessons learned from successes and failures.
Modulators of glucagon-like peptide 1 (GLP1) and the resulting G protein-coupled receptor (GPCR) signalling have recently come to the fore of the treatment of type 2 diabetes. In this Opinion article, Oh and Olefsky discuss the potential for intervention with other GPCRs for the treatment of this disease, highlighting GPCR-mediated effects on insulin secretion, insulin sensitivity and inflammation.
The conversion of cells with an epithelial phenotype into cells with a mesenchymal phenotype — epithelial–mesenchymal transition — has a key role in tumour progression and is therefore becoming a promising anticancer target. This article discusses the screening and classification of compounds that affect epithelial–mesenchymal transition, highlights some compounds of particular interest and discusses issues related to their clinical application.
