Irreversible kinase inhibitors gain traction doi:10.1038/nrd4103 The approval of Boehringer Ingelheim's anticancer drug afatinib highlights the growing enthusiasm for once-shunned irreversible kinase inhibitors. Full Text
Patient-focused drug development programme takes first steps doi:10.1038/nrd4104 First meetings see regulators and patient advocates start working to incorporate the perspective of patients into benefit-risk assessments. Full Text
Trial watch: Clinical trial boost for lentiviral gene therapy doi:10.1038/nrd4111 Two Phase I/II trials for two different rare diseases have highlighted the potential of using lentiviral vectors in haematopoetic stem cell gene therapy. Full Text
Regulatory watch: Speedy validation sought for new cardiotoxicity testing strategy doi:10.1038/nrd4112 The US FDA, the Health and Environmental Sciences Institute and the Cardiac Safety Research Consortium presented a new paradigm for cardiotoxicity testing, with a goal of validating and standardizing the new assays in 2 years’ time. Full Text
Sleuthing for toxicity doi:10.1038/scibx.2013.879 Researchers have determined that off-target toxicity most likely caused the two fatalities in a cancer trial of affinity-enhanced T cell receptors. The results highlight the need for using biologically appropriate disease models and deep molecular analyses to minimize cross-reactivity-related toxicity in future adoptive immunotherapy trials. Full Text
The epigenetics pipeline doi:10.1038/nrd4091 Epigenetic alterations are found in a number of diseases. This analysis explores the different approaches that are being pursued to exploit the therapeutic potential of epigenetic targets, and provides an overview of the current epigenetics pipeline. Full Text
HIV: Efficacy through BibNAbs doi:10.1038/nrd4109 Highly potent bispecific broadly neutralizing antibodies (bNAbs) against a broad range of HIV-1 strains show promise for passive immunization against virus. Full Text
Cancer: Special delivery service doi:10.1038/nrd4107 Brain-penetrating nanocarriers loaded with dithiazanine iodide, an FDA-approved antihelminthic, could be used for treating glioblastoma multiforme. Full Text
G protein-coupled receptors: A double attack on pain doi:10.1038/nrd4105 Ligands targeting a heteromer consisting of the µ-opioid receptor (the target of the analgesic morphine) and a second GPCR could overcome some of the limitations of morphine. Full Text
50 years of hurdles and hope in anxiolytic drug discovery doi:10.1038/nrd4075 This Review analyses the major trends from a database of published preclinical studies on novel anxiolytic agents in the past 50 years, highlighting issues that may have hampered progress and offering recommendations to improve anxiolytic drug discovery. Full Text
Disrupting proton dynamics and energy metabolism for novel cancer therapy doi:10.1038/nrc3579 This Review discusses the interplay among metabolism, hypoxia and pH regulation and whether pH-regulatory systems can be targeted for anticancer therapy. Full Text
Mitogen-activated protein kinases in innate immunity doi:10.1038/nri3495 This Review summarizes our current understanding of the regulation and function of mitogen-activated protein kinases (MAPKs) in innate immunity, as well as the mechanisms by which pathogens manipulate MAPK activation and the potential of targeting MAPK pathways for the treatment of inflammatory diseases. Full Text
Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond doi:10.1038/nrd4099 Sphingosine-1-phosphate (S1P) has a key role in the control of immune cell trafficking and is involved in disorders including cancer and inflammatory diseases. Here, Spiegel and colleagues discuss the ways in which S1P could be therapeutically targeted and highlight recent data from preclinical studies and clinical trials. Full Text
Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. Full Text
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