Drug Discovery

The importance of epigenetic processes in many diseases has been increasingly appreciated in the past decade. In their Review, Arrowsmith and colleagues focus on protein families that mediate epigenetic signalling pathways through histone acetylation and methylation, discussing their links with disease and recent progress in

Emerging strategies to simultaneously catalyse rewardable innovation in the field of medical devices and reduce health-care costs could also be applicable in drug development.

Following an FDA advisory committee vote to restart clinical development of nerve growth factor antagonists, could this novel class of analgesics still fulfil its once-anticipated potential?

Researchers are starting to use high-throughput genomic technologies to guide patients into trials of experimental cancer therapies, but is our understanding of the cancer genome ready yet?

PCSK9 inhibitor space starts to heat upA slew of results on lipid-lowering PCSK9-targeting mAbs, presented at the annual American College of Cardiology meeting in Chicago, highlighted one of the next big hopes for cardiologists.The lowdown: Proprotein convertase subtilisin kexin 9 (PCSK9) is

ThromboGenics has entered into a commercialization agreement with Alcon for its experimental therapeutic ocriplasmin, which has successfully completed Phase III trials for an eye disorder known as symptomatic vitreomacular adhesion (VMA). Under the terms of the agreement, Alcon will be granted rights to market the

Two studies published in The Lancet indicate that the interleukin-6 receptor (IL-6R) has a causal role in the development of coronary heart disease (Lancet379, 1214–1224; 2012; Lancet379, 1205–1213; 2012).IL-6 is a pro-inflammatory cytokine that has a

Drug dosage patent ban casts doubt on diagnosticsIn a unanimous decision, the US Supreme Court has held that methods of determining therapeutic doses of a drug, based on the measurement of drug metabolite levels, are not eligible for patent protection. “This potentially wide-ranging decision

Nearly 175 scientists and drug developers gathered in Lake Tahoe in March for a Keystone meeting on novel targets and new chemical space. Key topics on the programme included advances in epigenetics and toxicology, but some of the most interesting themes emerged unplanned. Conference co-organizer Stephen Frye, who works at the University of North Carolina in Chapel Hill, USA, but previously led discovery medicinal chemistry at GlaxoSmithKline, told Asher Mullard that one unexpected success was in highlighting the emerging capabilities of academic drug discoverers. Another theme, covered by SciBx, was the renewed interest in phenotypic screening (see go.nature.com/9l2mO8).

This article analyses the relationship between risk and the cost of capital for projects in different stages of drug development and describes a framework that could improve portfolio optimization strategies.

First disease-modifying drug approved in the United States for the treatment of cystic fibrosis in patients with a specific mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator.

The accumulation of amyloid-β (Aβ) in the brain of patients with Alzheimer's disease (AD) is hypothesized to initiate a cascade of events culminating in neuronal loss and dementia. However, therapeutic approaches designed to reduce the production or aggregation of Aβ in the brain have so

A paper in Nature Medicine shows that inhibitors of an enzyme involved in the epigenetic regulation of gene expression — lysine-specific demethylase 1 (LSD1; also known as KDM1A) — can make drug-insensitive forms of acute myeloid leukaemia (AML) responsive to treatment with all-trans

The build-up of misfolded α-synuclein is linked to neurodegeneration in Parkinson's disease and other so-called α-synucleinopathies, but how α-synuclein triggers neuronal death in vivo is unclear. Together, two studies from Lee and colleagues show that endoplasmic reticulum (ER) stress contributes to α-synuclein-linked neurodegeneration in

Many of us have tried to explain our research projects to a friend or relative and ended up summarizing with the unsatisfactory phrase, “well, it's...complicated”. That message is all too applicable in the translation of genomic findings in cancer cell lines to clinical therapies, but

Duchenne muscular dystrophy (DMD) is a debilitating genetic disorder in which muscles gradually degenerate and for which there are no effective treatments. Now, a study in Nature suggests that increasing the expression of heat shock protein 72 (HSP72) with the nicotinic amidoxime derivative BGP-15

Motor cytoplasmic dynein is an ATPase that regulates ciliary trafficking, mitotic spindle formation and organelle transport. Firestone et al. described the discovery of the first specific small-molecule antagonists of cytoplasmic dynein, termed ciliobrevins. They showed that ciliobrevins modulate protein trafficking within primary cilia, which

Gerlinger et al. conducted whole-exome sequencing of biopsy samples taken from different tumour regions from patients with renal cell carcinoma. They showed that the individual tumours displayed extensive intratumour heterogeneity. For example, 63–69% of somatic mutations were not detectable across every tumour region, several

This paper showed that FtsZ, a guanosine triphosphatase involved in bacterial cell division, is a new target for overcoming methicillin-resistant Staphylococcus aureus (MRSA) resistance to β-lactam antibiotics. The authors showed that the FtsZ-specific inhibitor PC190723 acts synergistically with a β-lactam antibiotic to reduce infection

Activation of T cell responses against multiple tumour-associated antigens could be beneficial in several types of cancer. This paper showed that injection of mice with virus-expressed cDNA libraries from melanocytes could cure established melanoma in 60% of mice, which was achieved through the priming of

Given its position at the heart of small-molecule drug discovery, medicinal chemistry has an important role in tackling the well-known productivity challenges in pharmaceutical research and development. In recent years, extensive analyses of successful and failed discovery compounds and drug candidates have improved our understanding

The mammalian proprotein convertases constitute a family of nine secretory serine proteases that are related to bacterial subtilisin and yeast kexin. Seven of these (proprotein convertase 1 (PC1), PC2, furin, PC4, PC5, paired basic amino acid cleaving enzyme 4 (PACE4) and PC7) activate cellular and

Epigenetic regulation of gene expression is a dynamic and reversible process that establishes normal cellular phenotypes but also contributes to human diseases. At the molecular level, epigenetic regulation involves hierarchical covalent modification of DNA and the proteins that package DNA, such as histones. Here, we

Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a

The declining productivity of drug research and development (R&D) analysed in an article by Paul and colleagues (How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nature Rev. Drug Discov.9, 203–214 (2010)) is of major

In their recent correspondence related to an interview discussing the Voluntary Harmonization Procedure (VHP) for the assessment of multinational clinical trials in the European Union (EU) (An audience with... Hartmut Krafft. Nature Rev. Drug Discov.9, 426 (2010)), Amexis

A recent news article discussed the progress in gene therapy, a field that has had a number of major setbacks (Gene therapies advance towards finish line. Nature Rev. Drug Discov.10, 719–720 (2011)). The recent

Neurological disorders: Nanoparticle opens door to cerebral palsy treatment Nature Reviews Drug Discovery. doi:10.1038/nrd3758 Author: Sarah Crunkhorn

Infectious disease: Pro-resolving lipids offer a helping hand to antibiotics Nature Reviews Drug Discovery. doi:10.1038/nrd3760 Author: Katrin Legg

Bone diseases: SEMA3A strikes a balance in bone homeostasis Nature Reviews Drug Discovery. doi:10.1038/nrd3759 Author: Man Tsuey Tse

A wealth of preclinical data on the role of neuropeptides in modulating behaviour has encouraged extensive efforts to target neuropeptide receptors for the treatment of psychiatric diseases, but so far clinical studies have not led to marketed drugs. This article analyses research on neuropeptide receptor ligands that have been studied in clinical trials, including agents that target the receptors for tachykinins, corticotropin-releasing factor and vasopressin, and suggests new ways to realize their full potential.

A blueprint for an ideal corporate information centre Nature Reviews Drug Discovery. doi:10.1038/nrd2973-c1 Authors: Oliver Renn, Michael Archer, Carmen Burkhardt, Jeannette Ginestet, Henning P. Nielsen, Joanna Woodward & the P-D-R Library Affairs & Copyright Group