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  • Principles for targeting RNA with drug-like small molecules
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-06
    Katherine Deigan Warner, Christine E. Hajdin, Kevin M. Weeks

    RNA molecules are essential for cellular information transfer and gene regulation, and RNAs have been implicated in many human diseases. Messenger and non-coding RNAs contain highly structured elements, and evidence suggests that many of these structures are important for function. Targeting these RNAs with small molecules offers opportunities to therapeutically modulate numerous cellular processes, including those linked to 'undruggable' protein targets. Despite this promise, there is currently only a single class of human-designed small molecules that target RNA used clinically — the linezolid antibiotics. However, a growing number of small-molecule RNA ligands are being identified, leading to burgeoning interest in the field. Here, we discuss principles for discovering small-molecule drugs that target RNA and argue that the overarching challenge is to identify appropriate target structures — namely, in disease-causing RNAs that have high information content and, consequently, appropriate ligand-binding pockets. If focus is placed on such druggable binding sites in RNA, extensive knowledge of the typical physicochemical properties of drug-like small molecules could then enable small-molecule drug discovery for RNA targets to become (only) roughly as difficult as for protein targets.

    更新日期:2018-07-08
  • Concerns, challenges and promises of high-content analysis of 3D cellular models
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-06
    Neil Carragher, Filippo Piccinini, Anna Tesei, O. Joseph Trask Jr, Marc Bickle, Peter Horvath

    Concerns, challenges and promises of high-content analysis of 3D cellular modelsConcerns, challenges and promises of high-content analysis of 3D cellular models, Published online: 06 July 2018; doi:10.1038/nrd.2018.99Concerns, challenges and promises of high-content analysis of 3D cellular models

    更新日期:2018-07-08
  • A call for a global 'bigger' data approach to Alzheimer disease
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-06
    Eric Perakslis, Henry Riordan, Lawrence Friedhoff, Azmi Nabulsi, Emilio Merlo Pich

    A call for a global 'bigger' data approach to Alzheimer diseaseA call for a global 'bigger' data approach to Alzheimer disease, Published online: 06 July 2018; doi:10.1038/nrd.2018.86Clinical trials for Alzheimer disease drugs have an exceptionally high failure rate, discouraging investment in the field despite the unmet medical need. Drug developers need to more effectively harness existing and emerging data and digital technologies to improve the likelihood of success.

    更新日期:2018-07-08
  • The evolution of adaptiveness: balancing speed and evidence
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-06
    Hans-Georg Eichler, Richard Barker, Nicola Bedlington, Jacoline C. Bouvy, André W. Broekmans, Anna Bucsics, Francesca Cerreta, Solange Corriol-Rohou, Alicia Granados, Yann Le Cam, Ad Schuurman

    The evolution of adaptiveness: balancing speed and evidenceThe evolution of adaptiveness: balancing speed and evidence, Published online: 06 July 2018; doi:10.1038/nrd.2018.90'Adaptive' approaches to bringing drugs to market have been widely discussed in recent years. Here, we describe the evolution of the adaptive approach and of concepts developed by ADAPT SMART, a multi-stakeholder consortium funded by the European Innovative Medicines Initiative.

    更新日期:2018-07-08
  • Lead identification: The importance of residual complexity
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Rebecca Kelsey

    Lead identification: The importance of residual complexityLead identification: The importance of residual complexity, Published online: 28 June 2018; doi:10.1038/nrd.2018.104Lead identification: The importance of residual complexity

    更新日期:2018-06-28
  • Infectious disease: Alphavirus receptor identified
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Sarah Crunkhorn

    Infectious disease: Alphavirus receptor identifiedInfectious disease: Alphavirus receptor identified, Published online: 28 June 2018; doi:10.1038/nrd.2018.106Infectious disease: Alphavirus receptor identified

    更新日期:2018-06-28
  • Market watch: Upcoming catalysts in Q3 2018
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Karen Nguyen

    Market watch: Upcoming catalysts in Q3 2018Market watch: Upcoming catalysts in Q3 2018, Published online: 28 June 2018; doi:10.1038/nrd.2018.108Market watch: Upcoming catalysts in Q3 2018

    更新日期:2018-06-28
  • FDA approves Eli Lilly's baricitinib
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Asher Mullard

    FDA approves Eli Lilly's baricitinibFDA approves Eli Lilly's baricitinib, Published online: 28 June 2018; doi:10.1038/nrd.2018.112FDA approves Eli Lilly's baricitinib

    更新日期:2018-06-28
  • Ebola outbreak prompts experimental drug rollout
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Asher Mullard

    Ebola outbreak prompts experimental drug rolloutEbola outbreak prompts experimental drug rollout, Published online: 28 June 2018; doi:10.1038/nrd.2018.114Ebola outbreak prompts experimental drug rollout

    更新日期:2018-06-28
  • Amy Abernethy
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28

    Amy AbernethyAmy Abernethy, Published online: 28 June 2018; doi:10.1038/nrd.2018.101Amy Abernethy, CSO at Flatiron Health, talks about how cleaned up and curated real-world data stands to transform clinical trials, drug regulation, competition in the health-care market and drug prices.

    更新日期:2018-06-28
  • First GPCR-directed antibody passes approval milestone
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Elie Dolgin

    First GPCR-directed antibody passes approval milestoneFirst GPCR-directed antibody passes approval milestone, Published online: 28 June 2018; doi:10.1038/nrd.2018.103Amgen's erenumab recently secured FDA approval as the first G protein-coupled receptor-targeted antibody. More of these biologics are on the way, despite remaining challenges.

    更新日期:2018-06-28
  • Cancer: Minimizing metastasis
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-28
    Sarah Crunkhorn

    Cancer: Minimizing metastasisCancer: Minimizing metastasis, Published online: 28 June 2018; doi:10.1038/nrd.2018.105Cancer: Minimizing metastasis

    更新日期:2018-06-28
  • Genome editing to 're-write' wrongs
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-22
    Mary Ellen Perry, Kayla M. Valdes, Elizabeth Wilder, Christopher P. Austin, Philip J. Brooks

    Genome editing to 're-write' wrongs Genome editing to 're-write' wrongs, Published online: 22 June 2018; doi:10.1038/nrd.2018.91 The NIH has launched the Somatic Cell Genome Editing (SCGE) programme to accelerate the development of safer and more effective genome-editing therapeutics.

    更新日期:2018-06-22
  • Stroke: Opening the therapeutic window
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-15
    Sarah Crunkhorn

    Stroke: Opening the therapeutic window Stroke: Opening the therapeutic window, Published online: 15 June 2018; doi:10.1038/nrd.2018.98 Stroke: Opening the therapeutic window

    更新日期:2018-06-15
  • The promise and challenges of immune agonist antibody development in cancer
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-15
    Patrick A. Mayes, Kenneth W. Hance, Axel Hoos

    Immune cell functions are regulated by co-inhibitory and co-stimulatory receptors. The first two generations of cancer immunotherapy agents consist primarily of antagonist antibodies that block negative immune checkpoints, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte protein 4 (CTLA4). Looking ahead, there is substantial promise in targeting co-stimulatory receptors with agonist antibodies, and a growing number of these agents are making their way through various stages of development. This Review discusses the key considerations and potential pitfalls of immune agonist antibody design and development, their differentiating features from antagonist antibodies and the landscape of agonist antibodies in clinical development for cancer treatment.

    更新日期:2018-06-15
  • The market for oral anticoagulants
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-15
    Stephen Bielecki, Dolim Lee, Bashar Hamad

    The market for oral anticoagulants The market for oral anticoagulants, Published online: 15 June 2018; doi:10.1038/nrd.2018.89 This article discusses the market for oral anticoagulants, and how therapies in development and antidotes to existing drugs could affect the therapeutic landscape.

    更新日期:2018-06-15
  • Infectious diseases: The painful path to avoiding the immune system
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-15
    M. Teresa Villanueva

    Infectious diseases: The painful path to avoiding the immune system Infectious diseases: The painful path to avoiding the immune system, Published online: 15 June 2018; doi:10.1038/nrd.2018.100 Infectious diseases: The painful path to avoiding the immune system

    更新日期:2018-06-15
  • Cancer: Re-educating tumour-associated macrophages with nanoparticles
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-15
    Megan Cully

    Cancer: Re-educating tumour-associated macrophages with nanoparticles Cancer: Re-educating tumour-associated macrophages with nanoparticles, Published online: 15 June 2018; doi:10.1038/nrd.2018.102 Cancer: Re-educating tumour-associated macrophages with nanoparticles

    更新日期:2018-06-15
  • Overcoming the legal and regulatory barriers to drug repurposing
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-08
    Alasdair Breckenridge, Robin Jacob

    Drug repurposing has been proposed as a strategy to develop new therapies that has fewer risks, lower costs and shorter timelines than developing completely new drugs. However, the potential of this strategy has not been as widely realized as hoped, in part owing to legal and regulatory barriers. Here, we highlight these barriers and consider how they could be overcome.

    更新日期:2018-06-08
  • Cryo-EM in drug discovery: achievements, limitations and prospects
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-08
    Jean-Paul Renaud, Ashwin Chari, Claudio Ciferri, Wen-ti Liu, Hervé-William Rémigy, Holger Stark, Christian Wiesmann

    Cryo-electron microscopy (cryo-EM) of non-crystalline single particles is a biophysical technique that can be used to determine the structure of biological macromolecules and assemblies. Historically, its potential for application in drug discovery has been heavily limited by two issues: the minimum size of the structures it can be used to study and the resolution of the images. However, recent technological advances — including the development of direct electron detectors and more effective computational image analysis techniques — are revolutionizing the utility of cryo-EM, leading to a burst of high-resolution structures of large macromolecular assemblies. These advances have raised hopes that single-particle cryo-EM might soon become an important tool for drug discovery, particularly if they could enable structural determination for 'intractable' targets that are still not accessible to X-ray crystallographic analysis. This article describes the recent advances in the field and critically assesses their relevance for drug discovery as well as discussing at what stages of the drug discovery pipeline cryo-EM can be useful today and what to expect in the near future.

    更新日期:2018-06-08
  • Advances and innovations in haemophilia treatment
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-08
    Rob Peters, Tim Harris

    Haemophilia is a rare disease for which the approved therapeutic options have remained virtually unchanged for 50 years. In the past decade, however, there has been an explosion of innovation in the treatment options that are either in development or have been approved for haemophilia, including engineered clotting factors and an extensive pipeline of new approaches and modalities. Several of these new modalities, especially gene therapy, demonstrate proof of principle in haemophilia but could have broader applications. These advances, in combination with better diagnostics, are now enabling clinicians to improve the standard of care for people with haemophilia. The different mechanisms of action and modifications used in these therapies have implications for their safe and efficacious use, which must be balanced with their therapeutic utility. This Review focuses on the biological aspects of the most advanced and innovative approaches for haemophilia treatment and considers their future use.

    更新日期:2018-06-08
  • Impact of the Innovative Medicines Initiative on vaccine development
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-06-01
    Philippe Denoel, Patricia Londoño-Hayes, Magda Chlebus, Magdalena Rodriguez de Azero

    Impact of the Innovative Medicines Initiative on vaccine development Impact of the Innovative Medicines Initiative on vaccine development, Published online: 01 June 2018; doi:10.1038/nrd.2018.72 Since its launch a decade ago, the European Innovative Medicines Initiative (IMI), a leading public–private partnership in life sciences, has catalysed scientific breakthroughs and the development of strategies to address complex challenges in various biomedical fields. Here, we discuss the progress of IMI projects related to vaccine research and development.

    更新日期:2018-06-01
  • Cancer: Restoring p53 activity
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Sarah Crunkhorn

    Cancer: Restoring p53 activity Cancer: Restoring p53 activity, Published online: 30 May 2018; doi:10.1038/nrd.2018.81 Cancer: Restoring p53 activity

    更新日期:2018-05-31
  • Autoimmune disease: Targeting glucose transport in psoriasis
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Sarah Crunkhorn

    Autoimmune disease: Targeting glucose transport in psoriasis Autoimmune disease: Targeting glucose transport in psoriasis, Published online: 30 May 2018; doi:10.1038/nrd.2018.79 Autoimmune disease: Targeting glucose transport in psoriasis

    更新日期:2018-05-31
  • Cancer: Personalized cancer vaccines hit the spot
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Megan Cully

    Cancer: Personalized cancer vaccines hit the spot Cancer: Personalized cancer vaccines hit the spot, Published online: 30 May 2018; doi:10.1038/nrd.2018.85 Cancer: Personalized cancer vaccines hit the spot

    更新日期:2018-05-31
  • Sepsis researchers set sights on immunotherapeutic strategies
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Asher Mullard

    Sepsis researchers set sights on immunotherapeutic strategies Sepsis researchers set sights on immunotherapeutic strategies, Published online: 30 May 2018; doi:10.1038/nrd.2018.87 Two immune-boosting strategies have independently indicated promise in sepsis clinical trials, after years of failures with anti-inflammatories in this same space. Will it be enough to take sepsis drug development out of 'critical condition'?

    更新日期:2018-05-31
  • On the origin of transformative drugs
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Asher Mullard

    On the origin of transformative drugs On the origin of transformative drugs, Published online: 30 May 2018; doi:10.1038/nrd.2018.95 On the origin of transformative drugs

    更新日期:2018-05-31
  • Liver disease: Reducing cancer risk
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Sarah Crunkhorn

    Liver disease: Reducing cancer risk Liver disease: Reducing cancer risk, Published online: 30 May 2018; doi:10.1038/nrd.2018.80 Liver disease: Reducing cancer risk

    更新日期:2018-05-31
  • Cancer: Preventing metastatic relapse
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30
    Sarah Crunkhorn

    Cancer: Preventing metastatic relapse Cancer: Preventing metastatic relapse, Published online: 30 May 2018; doi:10.1038/nrd.2018.78 Cancer: Preventing metastatic relapse

    更新日期:2018-05-31
  • Norbert Bischofberger
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-30

    Norbert Bischofberger Norbert Bischofberger, Published online: 30 May 2018; doi:10.1038/nrd.2018.82 Norbert Bischofberger, former CSO of Gilead, discusses antiviral opportunities, Gilead's pivot to oncology and the need for a societal discussion of drug costs.

    更新日期:2018-05-31
  • The global landscape of cancer cell therapy
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-25
    Jun Tang, Vanessa M. Hubbard-Lucey, Laura Pearce, Jill O'Donnell-Tormey, Aiman Shalabi

    The global landscape of cancer cell therapy The global landscape of cancer cell therapy, Published online: 25 May 2018; doi:10.1038/nrd.2018.74 How many cancer cell therapies are being developed? To harmonize efforts in this arena, the Cancer Research Institute has curated a database that includes all cell therapies in development.

    更新日期:2018-05-25
  • RNA-modifying proteins as anticancer drug targets
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-18
    P. Ann Boriack-Sjodin, Scott Ribich, Robert A. Copeland

    All major biological macromolecules (DNA, RNA, proteins and lipids) undergo enzyme-catalysed covalent modifications that impact their structure, function and stability. A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA stability and translation to proteins; these mechanisms of translational control have been termed epitranscriptomics. Emerging data suggest that some epitranscriptomic mechanisms are altered in human cancers as well as other human diseases. In this Review, we examine the current understanding of RNA modifications with a focus on mRNA methylation, highlight their possible roles in specific cancer indications and discuss the emerging potential of RNA-modifying proteins as therapeutic targets.

    更新日期:2018-05-18
  • Neuroscience: Reconnecting the brain after injury
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-18
    M. Teresa Villanueva

    Neuroscience: Reconnecting the brain after injury Neuroscience: Reconnecting the brain after injury, Published online: 18 May 2018; doi:10.1038/nrd.2018.83 Neuroscience: Reconnecting the brain after injury

    更新日期:2018-05-18
  • The haemophilia drug market
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-18
    Kerri Brown, Graeme Green

    The haemophilia drug market The haemophilia drug market, Published online: 18 May 2018; doi:10.1038/nrd.2018.54 This article discusses the market for therapies for haemophila, which is forecast to change substantially with the recent launch of emicizumab and the potential future approvals of gene therapies and non-factor treatments.

    更新日期:2018-05-18
  • Neurodegenerative disorders: Rescuing mitochondrial motility
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-18
    Sarah Crunkhorn

    Neurodegenerative disorders: Rescuing mitochondrial motility Neurodegenerative disorders: Rescuing mitochondrial motility, Published online: 18 May 2018; doi:10.1038/nrd.2018.76 Neurodegenerative disorders: Rescuing mitochondrial motility

    更新日期:2018-05-18
  • Antibacterial drugs: Disrupting MRSA 'persisters'
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-18
    Conor A. Bradley

    Antibacterial drugs: Disrupting MRSA 'persisters' Antibacterial drugs: Disrupting MRSA 'persisters', Published online: 18 May 2018; doi:10.1038/nrd.2018.84 Antibacterial drugs: Disrupting MRSA 'persisters'

    更新日期:2018-05-18
  • Post-exposure treatments for Ebola and Marburg virus infections
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-04
    Robert W. Cross, Chad E. Mire, Heinz Feldmann, Thomas W. Geisbert

    Post-exposure treatments for Ebola and Marburg virus infections Post-exposure treatments for Ebola and Marburg virus infections, Published online: 04 May 2018; doi:10.1038/nrd.2018.73 Post-exposure treatments for Ebola and Marburg virus infections

    更新日期:2018-05-04
  • Interleukin-6: designing specific therapeutics for a complex cytokine
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-05-04
    Christoph Garbers, Sylvia Heink, Thomas Korn, Stefan Rose-John

    Interleukin-6 (IL-6) is a pivotal cytokine with a diverse repertoire of physiological functions that include regulation of immune cell proliferation and differentiation. Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders such as rheumatoid arthritis and Castleman disease, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. So far, monoclonal antibodies against IL-6 or IL-6 receptor (IL-6R) and Janus kinases (JAK) inhibitors have been successfully developed for the treatment of autoimmune diseases such as rheumatoid arthritis. However, clinical trials of agents targeting IL-6 signalling have also raised questions about the diseases and patient populations for which such agents have an appropriate benefit–risk profile. Knowledge from clinical trials and advances in our understanding of the complexities of IL-6 signalling, including the potential to target an IL-6 trans-signalling pathway, are now indicating novel opportunities for therapeutic intervention. In this Review, we overview the roles of IL-6 in health and disease and analyse progress with several approaches of inhibiting IL-6-signalling, with the aim of illuminating when and how to apply IL-6 blockade.

    更新日期:2018-05-04
  • Neurodegeneration: New strategy for SBMA therapy
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Sarah Crunkhorn

    Neurodegeneration: New strategy for SBMA therapy Neurodegeneration: New strategy for SBMA therapy, Published online: 27 April 2018; doi:10.1038/nrd.2018.55 Neurodegeneration: New strategy for SBMA therapy

    更新日期:2018-04-27
  • Malaria: Clues to vaccine design
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Sarah Crunkhorn

    Malaria: Clues to vaccine design Malaria: Clues to vaccine design, Published online: 27 April 2018; doi:10.1038/nrd.2018.57 Malaria: Clues to vaccine design

    更新日期:2018-04-27
  • Regulatory watch: FDA new drug approvals in Q1 2018
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Lisa Urquhart

    Regulatory watch: FDA new drug approvals in Q1 2018 Regulatory watch: FDA new drug approvals in Q1 2018, Published online: 27 April 2018; doi:10.1038/nrd.2018.61 Regulatory watch: FDA new drug approvals in Q1 2018

    更新日期:2018-04-27
  • Anticancer drugs: Flipping the switch for selective GSK3 inhibition
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Katie Kingwell

    Anticancer drugs: Flipping the switch for selective GSK3 inhibition Anticancer drugs: Flipping the switch for selective GSK3 inhibition, Published online: 27 April 2018; doi:10.1038/nrd.2018.63 Anticancer drugs: Flipping the switch for selective GSK3 inhibition

    更新日期:2018-04-27
  • Microglia-targeted candidates push the Alzheimer drug envelope
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Asher Mullard

    Microglia-targeted candidates push the Alzheimer drug envelope Microglia-targeted candidates push the Alzheimer drug envelope, Published online: 27 April 2018; doi:10.1038/nrd.2018.65 Denali Therapeutics is taking a swing at neuroinflammation with a first-in-man trial of a RIPK1 inhibitor, while the company and others search for ways to target microglial biology more precisely.

    更新日期:2018-04-27
  • The expanding role of prodrugs in contemporary drug design and development
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Jarkko Rautio, Nicholas A. Meanwell, Li Di, Michael J. Hageman

    Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two. Prodrugs have evolved from being serendipitously discovered or used as a salvage effort to being intentionally designed. Such efforts can avoid drug development challenges that limit formulation options or result in unacceptable biopharmaceutical or pharmacokinetic performance, or poor targeting. In the past 10 years, the US Food and Drug Administration has approved at least 30 prodrugs, which accounts for more than 12% of all approved small-molecule new chemical entities. In this Review, we highlight prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs. We also discuss preclinical and clinical challenges and considerations in prodrug design and development.

    更新日期:2018-04-27
  • IDO takes a blow
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Asher Mullard

    IDO takes a blow IDO takes a blow, Published online: 27 April 2018; doi:10.1038/nrd.2018.67 IDO takes a blow

    更新日期:2018-04-27
  • Cashing in with off-the-shelf CAR Ts
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-27
    Asher Mullard

    Cashing in with off-the-shelf CAR Ts Cashing in with off-the-shelf CAR Ts, Published online: 27 April 2018; doi:10.1038/nrd.2018.69 Cashing in with off-the-shelf CAR Ts

    更新日期:2018-04-27
  • Metabolic disease: Liver enzyme inflames fat
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    Sarah Crunkhorn

    Metabolic disease: Liver enzyme inflames fat Metabolic disease: Liver enzyme inflames fat, Published online: 20 April 2018; doi:10.1038/nrd.2018.59 Metabolic disease: Liver enzyme inflames fat

    更新日期:2018-04-20
  • Cancer: Mopping up a molecule for breast cancer survival
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    Megan Cully

    Cancer: Mopping up a molecule for breast cancer survival Cancer: Mopping up a molecule for breast cancer survival, Published online: 20 April 2018; doi:10.1038/nrd.2018.58 Cancer: Mopping up a molecule for breast cancer survival

    更新日期:2018-04-20
  • Cancer immunotherapy: The perfect match
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    M. Teresa Villanueva

    Cancer immunotherapy: The perfect match Cancer immunotherapy: The perfect match, Published online: 20 April 2018; doi:10.1038/nrd.2018.62 Cancer immunotherapy: The perfect match

    更新日期:2018-04-20
  • Accelerating the development of therapeutic strategies for drug-resistant tuberculosis
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    Michael J. Vjecha, Simon Tiberi, Alimuddin Zumla

    Accelerating the development of therapeutic strategies for drug-resistant tuberculosis Accelerating the development of therapeutic strategies for drug-resistant tuberculosis, Published online: 20 April 2018; doi:10.1038/nrd.2018.64 Accelerating the development of therapeutic strategies for drug-resistant tuberculosis

    更新日期:2018-04-20
  • Translating translation
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    Christopher P. Austin

    Translating translation Translating translation, Published online: 20 April 2018; doi:10.1038/nrd.2018.27 The term 'translation' has emerged as a dominant concept in biomedical science over the last decade, but confusion around what the term means, and how it differs from translational research and translational science, is common. This article aims to help address this issue by clarifying the distinctions.

    更新日期:2018-04-20
  • What drives site performance in clinical trials?
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-20
    Brendan Smith, Linda Martin, Scott Martin, Maria Denslow, Melissa Hutchens, Conrad Hawkins, Valery Panier, Michael S. Ringel

    What drives site performance in clinical trials? What drives site performance in clinical trials?, Published online: 20 April 2018; doi:10.1038/nrd.2018.51 This article highlights results from a comprehensive study of the performance of clinical trial sites, which could help companies understand the underlying drivers of success.

    更新日期:2018-04-20
  • Senotherapeutics for healthy ageing
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-13
    Laura J. Niedernhofer, Paul D. Robbins

    Senotherapeutics for healthy ageing Senotherapeutics for healthy ageing, Published online: 13 April 2018; doi:10.1038/nrd.2018.44 Senotherapeutics for healthy ageing

    更新日期:2018-04-13
  • Chemical probes and drug leads from advances in synthetic planning and methodology
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-13
    Christopher J. Gerry, Stuart L. Schreiber

    Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by populating small-molecule libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. Drawing from more than a decade's worth of examples, we highlight how the design and synthesis of such libraries have been enabled by modern synthetic chemistry, and we illustrate the impact of the resultant chemical probes and drug leads in a wide range of diseases.

    更新日期:2018-04-13
  • INFORMED: an incubator at the US FDA for driving innovations in data science and agile technology
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-06
    Sean Khozin, Richard Pazdur, Anand Shah

    INFORMED: an incubator at the US FDA for driving innovations in data science and agile technology INFORMED: an incubator at the US FDA for driving innovations in data science and agile technology, Published online: 06 April 2018; doi:10.1038/nrd.2018.34 Information Exchange and Data Transformation (INFORMED), a multidisciplinary initiative anchored in the FDA Oncology Center of Excellence, is a decentralized science and technology incubator designed to harness the power of big data and advanced analytics to improve disease outcomes.

    更新日期:2018-04-06
  • The gastroesophageal cancer drug market
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-04-03
    Paul Wilcock, Rachel M. Webster

    The gastroesophageal cancer drug market The gastroesophageal cancer drug market, Published online: 03 April 2018; doi:10.1038/nrd.2018.35 Immune checkpoint inhibitors are forecast to expand the market for gastroesophageal cancer drugs, which is particularly large in Asia.

    更新日期:2018-04-03
  • Infectious disease: Virus-based tuberculosis vaccine
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-03-28
    Sarah Crunkhorn

    Infectious disease: Virus-based tuberculosis vaccine Infectious disease: Virus-based tuberculosis vaccine, Published online: 28 March 2018; doi:10.1038/nrd.2018.50 Infectious disease: Virus-based tuberculosis vaccine

    更新日期:2018-03-28
  • Immunotherapy: iPSC-based cancer vaccine
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-03-28
    Sarah Crunkhorn

    Immunotherapy: iPSC-based cancer vaccine Immunotherapy: iPSC-based cancer vaccine, Published online: 28 March 2018; doi:10.1038/nrd.2018.48 Immunotherapy: iPSC-based cancer vaccine

    更新日期:2018-03-28
  • George Yancopoulos
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-03-28

    George Yancopoulos George Yancopoulos, Published online: 28 March 2018; doi:10.1038/nrd.2018.41 George Yancopoulos, CSO of Regeneron, discusses his 30 years at Regeneron, the company's evolving growth plans and the recent launch of a precompetitive collaboration to sequence 500,000 UK Biobank exomes.

    更新日期:2018-03-28
  • Neurodevelopmental disorders: CRISPR to the rescue
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-03-28
    M. Teresa Villanueva

    Neurodevelopmental disorders: CRISPR to the rescue Neurodevelopmental disorders: CRISPR to the rescue, Published online: 28 March 2018; doi:10.1038/nrd.2018.39 Neurodevelopmental disorders: CRISPR to the rescue

    更新日期:2018-03-28
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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