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Preview: Nature Reviews Drug Discovery - Issue - nature.com science feeds

Nature Reviews Drug Discovery





 



Accelerating development of scientific evidence for medical products within the existing US regulatory framework

2017-02-24

Growing access to diverse 'real-world' data sources is enabling new approaches to close persistent evidence gaps about the optimal use of medical products in real-world practice. Here, we argue that contrary to widespread impressions, existing FDA regulations embody sufficient flexibility to accommodate the emerging tools



Nine paths to PCSK9 inhibition

2017-04-28

A lipid-modulating protein that exemplifies the value of human genetics for target validation has provided a fertile testing ground for new drug modalities including long-acting RNA interference drugs, vaccines against self-antigens, CRISPR therapeutics and small molecules that control ribosomal activity.



CAR T therapies drive into new terrain

2017-04-28

The FDA could soon approve the first chimeric antigen receptor (CAR) T therapies for blood cancers, but this young field is still working on how to address solid tumours, safety concerns and manufacturing issues.



FDA approves first drug for primary progressive multiple sclerosis

2017-04-28

The FDA approved Roche's ocrelizumab for the treatment of relapsing and primary progressive multiple sclerosis (PPMS), wrapping up a 40-year development history for the anti-CD20 monoclonal antibody (mAb). This is the first drug approval for PPMS, a form of the neurodegenerative disease that



FDA approves first deuterated drug

2017-04-28

The FDA approved Teva Pharmaceuticals' deutetrabenazine for chorea associated with Huntington disease, providing the first approval of a drug that contains the heavy hydrogen isotope deuterium.Early adopters first started tinkering with the use of deuterium in drug candidates more than 50 years ago.



FDA approves dupilumab for severe eczema

2017-04-28

The FDA approved Regeneron and Sanofi's first-in-class candidate dupilumab for the treatment of moderate-to-severe eczema.T helper 2 type responses have emerged as a unifying feature of various inflammatory and allergic diseases, such as eczema and asthma. As a result, type 2 cytokines —



Regulatory watch: From big data to smart data: FDA's INFORMED initiative

2017-02-24

Recent advances in our understanding of disease mechanisms have led to the development of new drugs that are enabling precision medicine. For example, the co-development of kinase inhibitors that target 'driver mutations' in metastatic non-small-cell lung cancer (NSCLC) with companion diagnostics has led to substantial



Trial watch: Trends in clinical trial design complexity

2017-04-18

The challenges of measuring the safety and efficacy of investigational drugs that target chronic, difficult-to-treat or rare diseases in more narrowly defined patient subpopulations have increased the scope of clinical trials and the burden to execute them in the past 15 years. Other factors affecting



Thomas Lynch

2017-04-28

Bristol-Myers Squibb has one of the deepest immuno-oncology drug pipelines, with checkpoint inhibitors, T cell and natural killer cell agonists, and metabolic modulators of the tumour microenvironment. Despite a setback with its marketed checkpoint inhibitor nivolumab in a first-line lung cancer setting last year, there are still high hopes for these emerging therapies. In March, the company hired Thomas Lynch — former CEO of Massachusetts General Physicians Organization and Director of the Yale Cancer Center — as its new Chief Scientific Officer, tasked with overseeing the progress of this pipeline. He told Asher Mullard about his R&D priorities, the promise of genomic-based diagnostics and the need for faster development of novel cancer drugs in earlier stages of disease.



Trends in the market for antihypertensive drugs

2017-03-10

This analysis provides an overview of novel antihypertensive products, many of which are fixed-dose combinations of different drug classes, and provides an outlook on their likely impact on the market.



Analgesia: Designing out opioid side effects

2017-04-18

Although opioids are very effective in treating pain that is associated with tissue damage and inflammation, they have important adverse effects, such as drowsiness, constipation, potential respiratory arrest and addiction. By analysing drug–opioid receptor interactions in damaged tissues, as opposed to healthy tissues, Stein and



Metabolic Disease: Protein tyrosine phosphatase inhibitor reverses diabetes

2017-04-21

The development of oral insulin-sensitizing agents to minimize the need for injectable insulin remains a major unmet need in the treatment of diabetes. Now, writing in Nature Chemical Biology, Bottini and colleagues report the identification of the first orally available small-molecule inhibitor of the



Cancer: Belt and braces for BCR–ABL

2017-04-21

The breakpoint cluster region–Abelson tyrosine kinase (BCR–ABL) fusion oncoprotein drives chronic myeloid leukaemia (CML). Although therapies targeting BCR–ABL — such as the pioneering compound imatinib — have dramatically improved patient outcomes, many patients need to remain on treatment, and drug resistance can emerge. Writing in



Anticancer therapy: Re-educating macrophages

2017-04-28

Despite being the main effectors of the innate immune response and programmed to detect and eliminate mutated cells, macrophages can change their phenotype and become pro-tumorigenic in response to cues from the tumour. Given their position within the tumour mass, tumour-associated macrophages (TAMs) are an



Antibiotics: Reversing resistance

2017-04-18

Acquired Mycobacterium tuberculosis resistance to the commonly used antibiotic ethionamide (ETH) is mediated by mutations in the bacterial enzymatic pathway that is required for biological activation of the drug. Here, Blondiaux et al. identify a series of spiroisoxazoline compounds — named small molecules



Viral infections: Targeting host kinases

2017-04-18

Targeting host pathways that are exploited by viruses represents a promising antiviral strategy. Bekerman et al. show that the host cell kinases AP2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK), which activate the host adapter proteins AP1 and AP2, are required by



Cancer: Identifying synergistic drug combinations

2017-04-18

Drug combinations are commonly used to counter drug resistance in cancer therapy. To identify synergistic drug target combinations, Han et al. have developed a scalable CRISPR-based double-knockout system that enables parallel pairwise gene knockout. Application of this system in a chronic myeloid leukaemia (CML)



G protein-coupled receptors: Novel probe for MRGPRX2

2017-04-18

The orphan MAS-related G protein-coupled receptor member X2 (MRGPRX2) is expressed primarily in human dorsal root ganglia and mast cells, and has been suggested to modulate pain and itch. Using a high-throughput screen of 5,695 unique compounds, Lansu et al. discovered that many exogenous



Regenerative medicine: Targeting adaptor protein interactions for nerve regrowth

2017-04-28

CNS neurons show limited capacity for spontaneous repair after injury, which hampers functional recovery in conditions such as stroke and traumatic brain injury. Now, a study in Neuron has shown that a small molecule, fusicoccin A (FC-A), promotes axon growth after injury in mice



Strategies and challenges for the next generation of antibody–drug conjugates

2017-03-17

Antibody–drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60



Advances in islet encapsulation technologies

2016-12-23

Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage



Targeting phospholipase D in cancer, infection and neurodegenerative disorders

2017-02-17

Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated



Bracing for the biosimilar wave

2017-03-31

Nature Reviews Drug Discovery16, 152–154 (2017)The article has been updated to indicate that Sandoz ran a confirmatory study in chronic plaque psoriasis of its etanercept biosimilar versus active comparator, rather than versus placebo.



Advances in islet encapsulation technologies

2017-04-28

Nature Reviews Drug Discovery, doi:10.1038/nrd.2016.232In this article, the University of Edmonton was referred to instead of the University of Alberta and the article cited as reference 10 was incorrect. These errors have been corrected in the online version.



An audience with Jay Bradner

2017-04-18

Nature Reviews Drug Discovery16, 232–233 (2017)Two typographical errors that may have affected the meaning of the answers related to the creation of the Chemical Biology & Therapeutics unit within NIBR and the focus of the NIBR leadership