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  • Heart regeneration and repair after myocardial infarction: translational opportunities for novel therapeutics
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-21
    Thomas J. Cahill, Robin P. Choudhury, Paul R. Riley

    Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix. These findings have revealed novel pathways that could be therapeutically targeted to stimulate repair following myocardial infarction and have provided lessons to guide future efforts towards heart regeneration through cellular reprogramming or cardiomyocyte transplantation.

    更新日期:2017-07-22
  • Senescent cells: an emerging target for diseases of ageing
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-21
    Bennett G. Childs, Martina Gluscevic, Darren J. Baker, Remi-Martin Laberge, Dan Marquess, Jamie Dananberg, Jan M. van Deursen

    Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.

    更新日期:2017-07-22
  • Opportunities for therapeutic antibodies directed at G-protein-coupled receptors
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-14
    Catherine J. Hutchings, Markus Koglin, William C. Olson, Fiona H. Marshall

    G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases. The progress made by targeting GPCRs with antibody-based therapeutics, as well as technical hurdles to overcome, are presented and discussed in this Review. Antibody therapeutics targeting C-C chemokine receptor type 4 (CCR4), CCR5 and calcitonin gene-related peptide (CGRP) are used as illustrative clinical case studies.

    更新日期:2017-07-14
  • Market watch: Strategies for biosimilars in emerging markets
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-07
    Ajay Gautam

    更新日期:2017-07-08
  • What is the right amount to spend on biopharma R&D?
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-07
    Michael S. Ringel

    This analysis investigates whether some companies may be negatively affecting their overall commercial success by aiming to maintain steady earnings per share growth and/or a target ratio of R&D spending to sales.

    更新日期:2017-07-08
  • Remyelination therapies: a new direction and challenge in multiple sclerosis
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-07
    Jason R. Plemel, Wei-Qiao Liu, V. Wee Yong

    Multiple sclerosis is characterized by inflammatory activity that results in destruction of the myelin sheaths that enwrap axons. The currently available medications for multiple sclerosis are predominantly immune-modulating and do not directly promote repair. White matter regeneration, or remyelination, is a new and exciting potential approach to treating multiple sclerosis, as remyelination repairs the damaged regions of the central nervous system. A wealth of new strategies in animal models that promote remyelination, including the repopulation of oligodendrocytes that produce myelin, has led to several clinical trials to test new reparative therapies. In this Review, we highlight the biology of, and obstacles to, remyelination. We address new strategies to improve remyelination in preclinical models, highlight the therapies that are currently undergoing clinical trials and discuss the challenges of objectively measuring remyelination in trials of repair in multiple sclerosis.

    更新日期:2017-07-08
  • Opportunities and challenges in phenotypic drug discovery: an industry perspective
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-07-07
    John G. Moffat, Fabien Vincent, Jonathan A. Lee, Jörg Eder, Marco Prunotto

    There has been a resurgence in interest in phenotypic drug discovery (PDD) approaches in recent years based on their potential to address the incompletely understood complexity of diseases and their promise of delivering first-in-class drugs. However, PDD approaches can also present considerable challenges, and this article focuses on the lessons learned by researchers engaged in PDD in the pharmaceutical industry, and discusses how PDD can best deliver value to drug discovery portfolios.

    更新日期:2017-07-08
  • Implications of cancer evolution for drug development
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-04-28
    Samra Turajlic, Charles Swanton

    Tumour evolution, which results in the existence of multiple distinct populations of cancer cells within the same tumour and the same patient, is increasingly appreciated to have a key role in drug resistance. In this article, we discuss the implications for drug development, including approaches to reduce the likelihood of the emergence of drug resistance.

    更新日期:2017-06-29
  • Chinese biopharma starts feeding the global pipeline
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Asher Mullard

    A handful of discovered-in-China candidates have entered the global clinic, including a few first-in-class contenders.

    更新日期:2017-06-29
  • Finding fault with Bial's fatal FAAH inhibitor
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Asher Mullard

    In January 2016, a phase I trial of Bial's oral analgesic BIA 10-2474 killed one volunteer and caused brain damage in four others. The fatal effects of the fatty acid amide hydrolase (FAAH) inhibitor may have been caused by off-target activity on several lipases,

    更新日期:2017-06-29
  • Genetic biomarker trumps tissue type in landmark oncology approval
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Asher Mullard

    The FDA granted accelerated approval to Merck & Co.'s PD1 blocker pembrolizumab for all cancers with a specific genetic biomarker, regardless of which tissue type is involved. “This is an important first for the cancer community,” said the FDA's Richard Pazdur, acting director of the

    更新日期:2017-06-29
  • Market watch: Landscape for medical countermeasure development
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-05
    Christopher Milne, Zachary Peter Smith, Ranjana Chakravarthy

    Medical countermeasures (MCMs) encompass biologics, drugs or devices that may be used for biodefence against biological, chemical or radiological bioweapons, or in the event of naturally occurring emerging and re-emerging diseases, or natural disasters. Since 2008, the Tufts Center for the Study of Drug Development

    更新日期:2017-06-29
  • Biotech R&D spending continues to rise
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Asher Mullard

    Biotech R&D spending hit US$45.7 billion in 2016, up 12% from 2015, found an annual analysis of the sector by consulting firm EY (see Fig. 1). This was the seventh consecutive year that these firms increased their cumulative R&D spending, and the second consecutive

    更新日期:2017-06-29
  • Yong-Jun liu
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29

    Yong-Jun Liu is a drug discovery veteran with a career that has spanned both academia and industry. Since 2002 he has overseen drug discovery programmes at the University of Texas MD Anderson Cancer Center, Baylor Research Institute and AstraZeneca's biologics company MedImmune. He added another large pharma firm to this roster in 2016, when he joined Sanofi as head of research. Sanofi's president of global R&D Elias Zerhouni prioritized the development-stage pipeline during the first years of his tenure at the company, but brought Liu on board last year to refocus on the internal early-stage drug discovery efforts. Liu spoke with Asher Mullard about his first year at Sanofi and the company's emphasis on multi-targeted therapeutics.

    更新日期:2017-06-29
  • Market watch: Upcoming market catalysts in Q3 2017
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sonny Nghiem

    Market catalysts in the third quarter of 2017 include top-line phase III trial results for several therapeutics: patisiran (developed by Alnylam Pharmaceuticals) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN); durvalumab (developed by AstraZeneca) for the first-line treatment of locally advanced or metastatic

    更新日期:2017-06-29
  • Cardiovascular disease: BET inhibitor attenuates heart failure
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Megan Cully

    Heart failure (HF) is a leading cause of mortality and hospitalization. Writing in Science Translational Medicine, Duan and colleagues demonstrate that inhibition of bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extraterminal domain (BET) family of epigenetic signalling proteins, reduces pathology and

    更新日期:2017-06-29
  • The ovarian cancer drug market
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-26
    Jennifer Bamford, Rachel M. Webster

    This article discusses the impact of the recent approvals of poly ADP ribose polymerase (PARP) inhibitors on the market for ovarian cancer drugs, as well as potential future treatments such as immunotherapies.

    更新日期:2017-06-29
  • Transporters: Natural product provides alternative transport for iron
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    Katie Kingwell

    Deficiencies in passive ion-transport proteins give rise to a range of diseases, including anaemias, cystic fibrosis and cardiac arrhythmias. A recent paper in Science has demonstrated that a small-molecule natural product, hinokitiol, transports iron across cell membranes and restores iron handling in several animal

    更新日期:2017-06-29
  • Endocrinology: Reducing fat and building bone
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    Menopause — characterized by an increase in circulating levels of follicle-stimulating hormone (FSH) and a decline in oestrogen due to ovarian failure — is associated with loss of bone mass and increased visceral adiposity. Although treatments for osteoporosis and obesity exist, their use may be

    更新日期:2017-06-29
  • Cancer: Targeting MYC-driven translation
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    Overactivity of the transcription factor MYC plays a central part in the progression of multiple myeloma through upregulation of ribosome synthesis and translation activity. Using a high-throughput screening approach, Manier et al. have identified a series of synthetic analogues of the rocaglate natural product

    更新日期:2017-06-29
  • Cancer immunotherapy: Macrophages steal the show
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-29
    M. Teresa Villanueva

    The past decade has seen remarkable advances in tumour immunology due to extensive research on inhibition of programmed cell death protein 1 (PD1) — which is expressed on T cells — and its ligand PDL1, which is expressed on tumour cells. However, little is known

    更新日期:2017-06-29
  • G Protein-Coupled Receptors: Crystal structure of glucagon family receptors
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    The class B G protein-coupled receptors (GPCRs), glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R), have key roles in glucose homeostasis and therefore represent valuable drug targets for diabetes. Zhang et al. now report the crystal structure of the full-length human GCGR in

    更新日期:2017-06-29
  • Genetic disorders: Repurposing metformin in FXS
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    Fragile X syndrome (FXS) is caused by loss of the fragile X mental retardation 1 (FMR1) gene and is characterized by learning disabilities and cognitive impairment. Here, Gantois et al. have shown that injection of the type 2 diabetes therapeutic metformin for

    更新日期:2017-06-29
  • Ageing: Old bone removal
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    M. Teresa Villanueva

    Senescent cells (SNCs), which accumulate in many tissues with age, contribute to several age-related pathologies. Now, Elisseeff and colleagues have shown that the selective elimination of SNCs with a specific inhibitor (UBX0101) of the anti-apoptotic protein mouse double minute 2 (MDM2) can prevent and even

    更新日期:2017-06-29
  • Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-03-24
    Seth W. Dickey, Gordon Y. C. Cheung, Michael Otto

    The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways — the target of traditional antibiotics — intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner. Notably, development of antivirulence drugs requires an in-depth understanding of the roles that diverse virulence factors have in disease processes. In this Review, we outline the theory behind antivirulence strategies and provide examples of bacterial features that can be targeted by antivirulence approaches. Furthermore, we discuss the recent successes and failures of this paradigm, and new developments that are in the pipeline.

    更新日期:2017-06-29
  • Targeting glutamate signalling in depression: progress and prospects
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-03-17
    James W. Murrough, Chadi G. Abdallah, Sanjay J. Mathew

    Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders. In this Review, we discuss the progress made in the development of such modulators for the treatment of depression, and examine recent preclinical and translational studies that have investigated the mechanisms of action of glutamate-targeting antidepressants. Fundamental questions remain regarding the future prospects of this line of drug development, including questions concerning safety and tolerability, efficacy, dose–response relationships and therapeutic mechanisms.

    更新日期:2017-06-29
  • Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-19
    Lorenzo Galluzzi, José Manuel Bravo-San Pedro, Beth Levine, Douglas R. Green, Guido Kroemer

    Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.

    更新日期:2017-06-29
  • The multiple sclerosis market
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-23
    Anders Westad, Aditya Venugopal, Eric Snyder

    This article discusses the impact of new drugs on the market for multiple sclerosis, including the recently approved immunomodulatory drug ocrelizumab and drugs in development such as sphingosine 1-phosphate receptor modulators and neurorestorative agents.

    更新日期:2017-06-24
  • Ageing: Old bone removal
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    M. Teresa Villanueva

    更新日期:2017-06-17
  • Endocrinology: Reducing fat and building bone
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    更新日期:2017-06-17
  • G Protein-Coupled Receptors: Crystal structure of glucagon family receptors
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    更新日期:2017-06-17
  • Genetic disorders: Repurposing metformin in FXS
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    更新日期:2017-06-17
  • Cancer: Targeting MYC-driven translation
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sarah Crunkhorn

    更新日期:2017-06-17
  • Market watch: Upcoming market catalysts in Q3 2017
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-16
    Sonny Nghiem

    更新日期:2017-06-17
  • Breaking barriers to novel analgesic drug development
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-06-09
    Ajay S. Yekkirala, David P. Roberson, Bruce P. Bean, Clifford J. Woolf

    Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.

    更新日期:2017-06-09
  • Metabolic disease: PGC1α inhibition ameliorates diabetes
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Sarah Crunkhorn

    Peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α) plays a pivotal part in energy homeostasis and is involved in the regulation of gluconeogenesis. Using a cell-based high-throughput chemical screen, Sharabi et al. have identified a small molecule, SR-18292, that increases acetylation of PGC1α, which results in

    更新日期:2017-05-31
  • Market watch: Trends in pharmaceutical company R&D spending: 2005–2015
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-12
    Richa Dixit, Frank S. David

    Pharmaceutical industry trade groups commonly claim that growing revenues (supported by premium prices) are required to drive innovative R&D, whereas critics maintain that drug companies' outsized returns mainly support corporate infrastructures, fuel marketing budgets and enrich investors. In fact, both arguments are incompletely supported by

    更新日期:2017-05-31
  • FDA approves first targeted drug for acute myelogenous leukaemia
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Asher Mullard

    The FDA approved Novartis's FLT3 inhibitor midostaurin for acute myeloid leukaemia (AML). The multikinase inhibitor is the first targeted treatment for AML, and the first new FDA approval for AML in decades.The FLT3 kinase is mutated in around one-third of AML patients, and

    更新日期:2017-05-31
  • FDA approves first new ALS drug in over 20 years
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Asher Mullard

    The FDA approved Mitsubishi Tanabe Pharma's edaravone for amyotrophic lateral sclerosis (ALS), the first US approval for the deadly neurodegenerative disease since riluzole in 1995.ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles, affecting the ability

    更新日期:2017-05-31
  • Immuno-oncology upset in bladder cancer
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Asher Mullard

    Roche and Genentech's checkpoint inhibitor atezolizumab did not improve overall survival in a confirmatory phase III trial in patients with advanced bladder cancer. The FDA granted accelerated approval to the anti-programmed cell death protein 1 ligand 1 (PDL1) antibody for this indication in 2016

    更新日期:2017-05-31
  • Zeroing in on neurodegenerative α-synuclein
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Katie Kingwell

    In the search for the first disease-modifying therapy for Parkinson disease, drug developers are advancing α-synuclein-targeted agents into proof-of-concept clinical trials.

    更新日期:2017-05-31
  • Lessons from immuno-oncology: a new era for cancer nanomedicine?
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-03-17
    Wen Jiang, Hengfeng Yuan, Charles K. Chan, Christina A. von Roemeling, Zuoqin Yan, Irving L. Weissman, Betty Y. S. Kim

    Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some

    更新日期:2017-05-31
  • Infectious disease: Peroxin inhibitor treats Trypanosoma infection
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Sarah Crunkhorn

    Insect-borne Trypanosoma spp. parasites transmitted predominantly by the tsetse fly infect humans as well as livestock, which causes devastating diseases, such as human African trypanosomiasis (HAT) and Chagas disease. Current treatments for trypanosomiases are limited, can cause serious side effects and require long treatment

    更新日期:2017-05-31
  • Inflammation: Oncostatin M blockade attenuates colitis
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Sarah Crunkhorn

    Anti-tumour necrosis factor (TNF) antibodies represent established therapies for inflammatory bowel disease (IBD), but up to 40% of patients exhibit primary nonresponsiveness to anti-TNF agents, and resistance can develop. West et al. observe high levels of the cytokine oncostatin M (OSM) and its receptor

    更新日期:2017-05-31
  • Neurological disorders: DAMPening damage after stroke
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-19
    Megan Cully

    Much of the tissue injury that occurs following ischaemic stroke is caused by sterile inflammation, which lasts for about a week after the initial artery blockade. Shichita and colleagues have found that increasing transcription of macrophage scavenger receptor 1 (Msr1) reduced neurological deficits

    更新日期:2017-05-31
  • Ageing: A youthful reminder
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Darran Yates

    In rodents, the introduction of blood from young to old animals can reverse some of the negative effects that ageing exerts on CNS function, including detrimental changes in hippocampal function. However, it is not known which molecules found in young blood exert such effects or

    更新日期:2017-05-31
  • Neurodegenerative disorders: Ataxin 2 reduction rescues motor defects
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-19
    Sarah Crunkhorn

    Mutations in ATXN2, the gene encoding ataxin 2 — an RNA-binding protein found throughout the body with multiple roles in RNA metabolism — have been implicated in both amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). Writing in Nature, two new

    更新日期:2017-05-31
  • Cancer immunotherapy: T cells get a ride
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-19
    M. Teresa Villanueva

    Strategies that inhibit the immune checkpoint blockade (ICB) and reactivate T cells using monoclonal antibodies against programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) have been used to successfully treat immunogenic tumours, and recent efforts have focused on combining this approach with

    更新日期:2017-05-31
  • How much do clinical trials cost?
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-19
    Linda Martin, Melissa Hutchens, Conrad Hawkins, Alaina Radnov

    This article presents the findings of a recent analysis of the costs of clinical trials, providing benchmark data for companies to assess their performance, as well as indicating cost drivers.

    更新日期:2017-05-31
  • Birgitte Volck
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31

    Small patient populations are big business. In 2000, worldwide sales of orphan drugs for rare diseases accounted for just 6% of global prescription drug sales. Last year they accounted for US$114 billion in revenue and nearly 16% of total prescription drug sales, and they are on track to account for 21% of sales by 2022. For Birgitte Volck, head of rare disease R&D at GlaxoSmithKline, the explosion of this space has tracked with the arrival of a new era in rare disease drug discovery and development. She told Asher Mullard about how new drug modalities, the voice of the patient and genomics are reshaping the field.

    更新日期:2017-05-31
  • Deal watch: Neurokinin 3 receptor antagonist revival heats up with Astellas acquisition
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Megan Cully

    Japan's Astellas Pharma has announced that it will acquire the Belgian biotech Ogeda for up to [euro]800 million, including milestone payments (Fig. 1). Ogeda's sole clinical asset, fezolinetant, is a small-molecule inhibitor of the neurokinin 3 receptor (NK3R), for which the company reported

    更新日期:2017-05-31
  • Search for liquid biopsy grail points the way to drug discovery and development gems
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Chris Morrison

    An emerging technology for early cancer diagnosis could lead to innovative clinical trial strategies, novel drug combinations and new drug targets.

    更新日期:2017-05-31
  • Aptamers as targeted therapeutics: current potential and challenges
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-04-28
    Jiehua Zhou, John Rossi

    Nature Reviews Drug Discovery16, 181–202 (2017)Base Pair Biotechnologies and Apterna were omitted from Table 3 in this article. These have now been included.

    更新日期:2017-05-31
  • Targeting iron metabolism in drug discovery and delivery
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-02-03
    Bart J. Crielaard, Twan Lammers, Stefano Rivella

    Iron fulfils a central role in many essential biochemical processes in human physiology; thus, proper processing of iron is crucial. Although iron metabolism is subject to relatively strict physiological control, numerous disorders, such as cancer and neurodegenerative diseases, have recently been linked to deregulated iron homeostasis. Consequently, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments for these diseases. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents are likely to have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are currently available.

    更新日期:2017-05-31
  • Delivery technologies for genome editing
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-03-24
    Hao Yin, Kevin J. Kauffman, Daniel G. Anderson

    With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials.

    更新日期:2017-05-31
  • Cystic fibrosis: Thymosin α1 rescues CFTR activity
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Sarah Crunkhorn

    Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and is characterized by chronic lung inflammation. Romani et al. show that the naturally occurring polypeptide thymosin α1 — clinically used as an immunotherapeutic agent —

    更新日期:2017-05-31
  • Ageing: FOXO4 inhibition eliminates senescent cells
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-05-31
    Sarah Crunkhorn

    Senescent cells exhibit a pro-inflammatory phenotype, and are thought to accelerate ageing and the onset of age-related diseases. Baar et al. report a key role for forkhead box protein O4 (FOXO4) in maintaining senescent cell viability. In vitro, a FOXO4-derived peptide designed to

    更新日期:2017-05-31
  • Non-kinase targets of protein kinase inhibitors
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-03-10
    Lenka Munoz

    Kinome-wide profiling platforms have comprehensively identified the relevant kinases that are targeted by numerous protein kinase inhibitors. However, recent projects have begun to discover non-kinase targets of kinase inhibitors. These non-kinase targets can contribute to the desired or undesired activities of inhibitors, or act as silent bystanders. As a full awareness of a drug's mechanism of action is crucial for the interpretation of results and for successful preclinical and clinical drug development, these discoveries highlight the importance of understanding the pharmacology of kinase inhibitors beyond the kinome. In this Review, I discuss kinase inhibitors for which non-kinase targets have been identified and the application of emerging techniques to validate drug–target engagement in intact cells.

    更新日期:2017-05-31
  • Anticancer therapy: Re-educating macrophages
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-04-28
    M. Teresa Villanueva

    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

    更新日期:2017-05-29
  • FDA approves first deuterated drug
    Nat. Rev. Drug. Disc. (IF 57) Pub Date : 2017-04-28
    Asher Mullard

    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.

    更新日期:2017-05-29
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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