Drug Discovery

Recent advances in RNA biology have accelerated the progress of a new generation of molecular therapies based on RNA, with several agents now in advanced clinical trials. In our first Review, Kole and colleagues compare and contrast the mechanisms of action and effects of three

Genome-wide screening is anticipated to accelerate the development of personalized medicine by identifying and exploiting new associations between genomic variants and drug responses. However, this goal could be undermined if care is not taken to minimize the impact of pharmacogenomic associations that turn out to

The US FDA approved 30 new therapeutics last year, including 11 first-in-class agents.

Globalization of clinical trials plateaus?The off-shoring of clinical trials outside the United States and Europe may have hit a plateau.The lowdown: Over the past decade, drug sponsors have increasingly shifted clinical trial programmes from the United States and Europe to the rest

In one of the largest preclinical-stage deals ever, Abbott has agreed to pay US$400 million upfront to Reata Pharmaceuticals as part of an agreement to jointly develop and commercialize a series of second-generation oral antioxidant inflammation modulators (AIMs) with potential applications in cardiovascular disease, neurodegenerative

Preliminary clinical trial data recently presented at the American Society of Hematology meeting showed that the Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 was effective in treating in several types of B cell lymphoma. Furthermore, PCI-32765 is at the centre of a deal — worth up

Regeneron and Genentech's VEGF trap dispute settles... and continues Regeneron and Genentech have settled their patent dispute over Eylea (aflibercept) — a treatment for wet age-related macular degeneration — which was launched onto the US market in November 2011. But the biotech companies are still

Late last year Merck & Co. announced plans to spend US$1.5 billion to bolster research and development (R&D) in China, one of the industry's largest investments in the country to date. The firm's initial plans include, by 2014, the construction of an Asian R&D headquarters in Beijing and a doubling of their Chinese research staff count to 600 employees. Overseeing the expansion is RuiPing Dong, head of emerging markets R&D. Prior to joining Merck in 2010, Dong headed up Bristol-Myers Squibb's R&D efforts in Asia-Pacific and the emerging markets, and supervised AstraZeneca's oncology programmes. Speaking with Asher Mullard, he explains the strategy behind the Chinese R&D expansion.

This article discusses the drug pipeline for neuropathic pain, for which the market is forecast to grow by 50% by 2020.

In November 2011, ruxolitinib (Jakafi; Incyte/Novartis), a small-molecule inhibitor of Janus kinases, was approved by the US Food and Drug Administration for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythaemia vera myelofibrosis and post-essential thrombocythaemia myelofibrosis.

The maintenance of protein homeostasis (proteostasis) is vital for cell function and involves a tightly regulated network of pathways controlling the synthesis, folding, transport and degradation of proteins. Loss of proteostatic control can lead to the accumulation and aggregation of misfolded proteins — features that

Although preclinical studies suggest that fibroblast growth factor 21 (FGF21) might have disease-modifying properties in obesity and type 2 diabetes, recombinant FGF21 protein has poor pharmacokinetics, which precludes its clinical use. Now, writing in Science Translational Medicine, a group from Genentech describes the identification

The recurrence and mortality rate of patients with glioblastoma multiforme (GBM) is close to 100%. At present, therapy consists of surgical debulking of the tumour followed by radiation therapy and chemotherapy. Preclinical studies have shown that therapeutically engineered stem cells may be well suited to

The concept of drug-likeness — which is based on the observation that physicochemical properties of drugs, such as molecular mass and lipophilicity, tend to fall within a relatively narrow range of the possible values — is widely used to prioritize compounds in early-stage drug discovery.

Inhibiting the oncogenic kinase BCR–ABL1, which causes chronic myeloid leukaemia (CML), is a paradigm for clinically successful targeted therapy. However, drug-resistant mutations frequently emerge during clinical treatment. A new study shows that attempting to inhibit drug-resistant BCR–ABL1 mutants can result in a counterproductive activation of

Signalling mediated by transforming growth factor-β (TGFβ) is dysregulated in lung disorders such as emphysema. This study showed that blockade of TGFβ improved disease symptoms in a mouse model of cigarette smoke-induced emphysema. Administration of a TGFβ-specific neutralizing antibody prevented alveolar cell death, and improved

Cami et al. describe a computational network-based method for predicting adverse drug reactions (ADRs). They collected drug safety data from 2005 and used it to construct a network of known drug–ADR associations. This was used to train a logistic regression model to predict unknown

Cellular metabolism has a key role in the pathogenesis of Huntington's disease (HD), which is caused by the accumulation of mutant huntingtin protein (HTT). These two studies show that sirtuin 1 (SIRT1), an NAD-dependent protein deacetylase involved in the control of cellular metabolism, has neuroprotective

Evasion of apoptosis is one of the crucial acquired capabilities used by cancer cells to fend off anticancer therapies. Inhibitor of apoptosis (IAP) proteins exert a range of biological activities that promote cancer cell survival and proliferation. X chromosome-linked IAP is a direct inhibitor of

Here, we discuss three RNA-based therapeutic technologies exploiting various oligonucleotides that bind to RNA by base pairing in a sequence-specific manner yet have different mechanisms of action and effects. RNA interference and antisense oligonucleotides downregulate gene expression by inducing enzyme-dependent degradation of targeted mRNA. Steric-blocking

Studies of psychiatric disorders have traditionally focused on emotional symptoms such as depression, anxiety and hallucinations. However, poorly controlled cognitive deficits are equally prominent and severely compromise quality of life, including social and professional integration. Consequently, intensive efforts are being made to characterize the cellular

As summarized in a recent article (Antibacterial R&D incentives. Nature Rev. Drug Discov.10, 727–728 (2011)), numerous 'push' and 'pull' economic incentives have been proposed to rekindle the antibiotic pipeline. These have been the

Nature Reviews Drug Discovery10, 887–888 (2011) The spelling of Stephen Hoffman's name has been corrected online, as has his affiliation.

Nature Reviews Drug Discovery11, 37–51 (2012) 10.1038/nrd3591The page numbers of reference 180 in this article are incorrect; these should be 10686–10689. This has been corrected in the online version of the article.

Metabolic disease: Exercise hormone fights metabolic disease Nature Reviews Drug Discovery. doi:10.1038/nrd3686 Author: Sarah Crunkhorn

Neurodegenerative disease: Harnessing virus-mediated mitochondrial protection to combat neurodegeneration Nature Reviews Drug Discovery. doi:10.1038/nrd3688 Author: Monica Hoyos Flight

Viral disease: Steps towards an HCV vaccine Nature Reviews Drug Discovery. doi:10.1038/nrd3687 Author: Charlotte Harrison

An upcoming decision for Novartis's Bexsero — the first vaccine against meningococcus B — could substantiate reverse vaccinology.

This Perspective highlights the sources and functions as well as the evaluation of biomarkers that are useful in cancer, with a focus on those biomarkers that are most relevant for identifying patients who are likely to respond to a given therapy, and those biomarkers that are most effective for measuring patient response to therapy.

2011 in reflection Nature Reviews Drug Discovery. doi:10.1038/nrd3678 Author: Asher Mullard

A crucial role of the immune system in cancer progression and response to therapy has recently emerged. Here, Galluzzi and colleagues discuss the immune parameters that may predict the therapeutic response of patients to chemotherapeutics, and review the mechanisms by which current antineoplastic agents activate the immune system against cancer.

Interfacial inhibitors: targeting macromolecular complexes Nature Reviews Drug Discovery. doi:10.1038/nrd3665 Authors: Yves Pommier & Christophe Marchand