显示样式:     当前期刊: Nature Reviews Drug Discovery    加入关注       排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Delphine Charvin, Rossella Medori, Robert A. Hauser, Olivier Rascol

    Therapeutic strategies for Parkinson disease: beyond dopaminergic drugsTherapeutic strategies for Parkinson disease: beyond dopaminergic drugs, Published online: 12 October 2018; doi:10.1038/nrd.2018.184Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs

    更新日期:2018-10-12
  • Cancer stem cell pipeline flounders
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Ken Garber

    Cancer stem cell pipeline floundersCancer stem cell pipeline flounders, Published online: 12 October 2018; doi:10.1038/nrd.2018.157With clinical failures mounting and companies disinvesting, researchers are revising the cancer stem cell model.

    更新日期:2018-10-12
  • Therapeutic strategies targeting connexins
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Dale W. Laird, Paul D. Lampe

    The connexin family of channel-forming proteins is present in every tissue type in the human anatomy. Connexins are best known for forming clustered intercellular channels, structurally known as gap junctions, where they serve to exchange members of the metabolome between adjacent cells. In their single-membrane hemichannel form, connexins can act as conduits for the passage of small molecules in autocrine and paracrine signalling. Here, we review the roles of connexins in health and disease, focusing on the potential of connexins as therapeutic targets in acquired and inherited diseases as well as wound repair, while highlighting the associated clinical challenges.

    更新日期:2018-10-12
  • Patent watch: Selective GABAA receptor modulators: intellectual property landscape
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Cecilia Martin, Drew Lowery

    Patent watch: Selective GABAA receptor modulators: intellectual property landscapePatent watch: Selective GABA<sub>A</sub> receptor modulators: intellectual property landscape, Published online: 12 October 2018; doi:10.1038/nrd.2018.179Patent watch: Selective GABAA receptor modulators: intellectual property landscape

    更新日期:2018-10-12
  • Regulatory T cells in the treatment of disease
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Amir Sharabi, Maria G. Tsokos, Ying Ding, Thomas R. Malek, David Klatzmann, George C. Tsokos

    Regulatory T (Treg) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, Treg cells are compromised. Approaches to strengthen Treg cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing Treg cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, Treg cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of Treg cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating Treg cells in autoimmune disorders, transplantation and cancer.

    更新日期:2018-10-12
  • Drug repurposing: progress, challenges and recommendations
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-12
    Sudeep Pushpakom, Francesco Iorio, Patrick A. Eyers, K. Jane Escott, Shirley Hopper, Andrew Wells, Andrew Doig, Tim Guilliams, Joanna Latimer, Christine McNamee, Alan Norris, Philippe Sanseau, David Cavalla, Munir Pirmohamed

    Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.

    更新日期:2018-10-12
  • Painkilling anti-NGF antibodies stage phase III comeback
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Asher Mullard

    Painkilling anti-NGF antibodies stage phase III comebackPainkilling anti-NGF antibodies stage phase III comeback, Published online: 01 October 2018; doi:10.1038/nrd.2018.177Painkilling anti-NGF antibodies stage phase III comeback

    更新日期:2018-10-01
  • Malaria medicine box expands
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Asher Mullard

    Malaria medicine box expandsMalaria medicine box expands, Published online: 01 October 2018; doi:10.1038/nrd.2018.156With the FDA's approval of GlaxoSmithKline's tafenoquine, global health experts will at last have access to a long-awaited new treatment for Plasmodium vivax recurrence. Much-needed novel treatments for the more common Plasmodium falciparum are in phase II trials.

    更新日期:2018-10-01
  • Market watch: Upcoming market catalysts in Q4 2018
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Stephanie Arthan

    Market watch: Upcoming market catalysts in Q4 2018Market watch: Upcoming market catalysts in Q4 2018, Published online: 01 October 2018; doi:10.1038/nrd.2018.162Market watch: Upcoming market catalysts in Q4 2018

    更新日期:2018-10-01
  • Metabolic disease: Preventing fat uptake
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Sarah Crunkhorn

    Metabolic disease: Preventing fat uptakeMetabolic disease: Preventing fat uptake, Published online: 01 October 2018; doi:10.1038/nrd.2018.170Metabolic disease: Preventing fat uptake

    更新日期:2018-10-01
  • Cancer: Disrupting energy metabolism
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Sarah Crunkhorn

    Cancer: Disrupting energy metabolismCancer: Disrupting energy metabolism, Published online: 01 October 2018; doi:10.1038/nrd.2018.172Cancer: Disrupting energy metabolism

    更新日期:2018-10-01
  • Chi-Med scores key approval for 'discovered in China' cancer drug
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Asher Mullard

    Chi-Med scores key approval for 'discovered in China' cancer drugChi-Med scores key approval for 'discovered in China' cancer drug, Published online: 01 October 2018; doi:10.1038/nrd.2018.176Chi-Med scores key approval for 'discovered in China' cancer drug

    更新日期:2018-10-01
  • Ida Sim
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01

    Ida SimIda Sim, Published online: 01 October 2018; doi:10.1038/nrd.2018.178Ida Sim, Vivli co-founder and UCSF informatician, discusses the need for a neutral broker platform that can facilitate access to and analysis of industry and academic patient-level clinical trial data.

    更新日期:2018-10-01
  • Microfluidics platform lowers barrier to drug combination screening
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-10-01
    Asher Mullard

    Microfluidics platform lowers barrier to drug combination screeningMicrofluidics platform lowers barrier to drug combination screening, Published online: 01 October 2018; doi:10.1038/nrd.2018.161Nanodroplets promise to reduce the equipment, cost and time constraints of high-throughput screening, if researchers can overcome long-standing hurdles.

    更新日期:2018-10-01
  • Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-28
    Delphine Charvin, Rossella Medori, Robert A. Hauser, Olivier Rascol

    Existing therapeutic strategies for managing Parkinson disease (PD), which focus on addressing the loss of dopamine and dopaminergic function linked with degeneration of dopaminergic neurons, are limited by side effects and lack of long-term efficacy. In recent decades, research into PD pathophysiology and pharmacology has focused on understanding and tackling the neurodegenerative processes and symptomology of PD. In this Review, we discuss the challenges associated with the development of novel therapies for PD, highlighting emerging agents that aim to target cell death, as well as new targets offering a symptomatic approach to managing features and progression of the disease.

    更新日期:2018-09-28
  • Reforming China's drug regulatory system
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-28
    Lili Xu, Huijun Gao, Kenneth I. Kaitin, Liming Shao

    Reforming China's drug regulatory systemReforming China's drug regulatory system, Published online: 28 September 2018; doi:10.1038/nrd.2018.150Since 2015, the Chinese government has introduced numerous reforms with the aim of establishing a more scientific and efficient drug regulatory system, which are highlighted here.

    更新日期:2018-09-28
  • Targeting G protein-coupled receptor signalling by blocking G proteins
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-28
    Adrian P. Campbell, Alan V. Smrcka

    G protein-coupled receptors (GPCRs) are the largest class of drug targets, largely owing to their druggability, diversity and physiological efficacy. Many drugs selectively target specific subtypes of GPCRs, but high specificity for individual GPCRs may not be desirable in complex multifactorial disease states in which multiple receptors may be involved. One approach is to target G protein subunits rather than the GPCRs directly. This approach has the potential to achieve broad efficacy by blocking pathways shared by multiple GPCRs. Additionally, because many GPCRs couple to multiple G protein signalling pathways, blocking specific G protein subunits can 'bias' GPCR signals by inhibiting only a subset of these signals. Molecules that target G protein α or βγ-subunits have been developed and show strong efficacy in multiple preclinical disease models and biased inhibition of G protein signalling. In this Review, we discuss the development and characterization of G protein α and βγ-subunit ligands and the preclinical evidence that this exciting new approach has potential for therapeutic efficacy in a number of indications, such as pain, thrombosis, asthma and heart failure.

    更新日期:2018-09-28
  • Neurodegenerative diseases: Ropin' in ALS
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-21
    Megan Cully

    Neurodegenerative diseases: Ropin' in ALSNeurodegenerative diseases: Ropin' in ALS, Published online: 21 September 2018; doi:10.1038/nrd.2018.163Neurodegenerative diseases: Ropin' in ALS

    更新日期:2018-09-21
  • Ageing: Reversing muscle degeneration
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-21
    Sarah Crunkhorn

    Ageing: Reversing muscle degenerationAgeing: Reversing muscle degeneration, Published online: 21 September 2018; doi:10.1038/nrd.2018.160Ageing: Reversing muscle degeneration

    更新日期:2018-09-21
  • Cancer immunotherapy: When a CAR becomes a tank
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-21
    M. Teresa Villanueva

    Cancer immunotherapy: When a CAR becomes a tankCancer immunotherapy: When a CAR becomes a tank, Published online: 21 September 2018; doi:10.1038/nrd.2018.164Cancer immunotherapy: When a CAR becomes a tank

    更新日期:2018-09-21
  • Genetic disorders: Bacterial therapeutic steps into the breach
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-21
    Katie Kingwell

    Genetic disorders: Bacterial therapeutic steps into the breachGenetic disorders: Bacterial therapeutic steps into the breach, Published online: 21 September 2018; doi:10.1038/nrd.2018.166Genetic disorders: Bacterial therapeutic steps into the breach

    更新日期:2018-09-21
  • Therapeutic approaches to Huntington disease: from the bench to the clinic
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-21
    Nicholas S. Caron, E. Ray Dorsey, Michael R. Hayden

    The 25 years since the identification of the gene responsible for Huntington disease (HD) have stood witness to profound discoveries about the nature of the disease and its pathogenesis. Despite this progress, however, the development of disease-modifying therapies has thus far been slow. Preclinical validation of the therapeutic potential of disrupted pathways in HD has led to the advancement of pharmacological agents, both novel and repurposed, for clinical evaluation. The most promising therapeutic approaches include huntingtin (HTT) lowering and modification as well as modulation of neuroinflammation and synaptic transmission. With clinical trials for many of these approaches imminent or currently ongoing, the coming years are promising not only for HD but also for more prevalent neurodegenerative disorders, such as Alzheimer and Parkinson disease, in which many of these pathways have been similarly implicated.

    更新日期:2018-09-21
  • Defining orphan conditions in the context of the European orphan regulation: challenges and evolution
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-12
    Daniel J. O'Connor, Maria E. Sheean, Matthias P. Hofer, Stelios Tsigkos, Segundo Mariz, Laura Fregonese, Kristina Larsson, Virginie Hivert, Kerstin Westermark, Frauke Naumann-Winter, Violeta Stoyanova-Beninska, Ingeborg Barišić, Giuseppe Capovilla, Armando Magrelli, Bruno Sepodes

    The definition and acceptability of an orphan condition is pivotal for the assessment of European orphan medicinal product designation applications, and consequently the eligibility for incentives. Here, based on the experiences of the Committee for Orphan Medicinal Products, we discuss how to define orphan conditions in the context of the European regulatory framework.

    更新日期:2018-09-12
  • Gene therapy for neurological disorders: progress and prospects
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-12
    Benjamin E. Deverman, Bernard M. Ravina, Krystof S. Bankiewicz, Steven M. Paul, Dinah W. Y. Sah

    Gene therapy for neurological disorders: progress and prospectsGene therapy for neurological disorders: progress and prospects, Published online: 12 September 2018; doi:10.1038/nrd.2018.158Gene therapy for neurological disorders: progress and prospects

    更新日期:2018-09-12
  • An RNA toolbox for cancer immunotherapy
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-09-07
    Fernando Pastor, Pedro Berraondo, Iñaki Etxeberria, Josh Frederick, Ugur Sahin, Eli Gilboa, Ignacio Melero

    Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules. These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to reach more efficient and personalized results. RNA and RNA derivatives can be exploited therapeutically as a platform to encode protein sequences, provide innate pro-inflammatory signals to the immune system (such as those denoting viral infection), control the expression of other RNAs (including key immunosuppressive factors) post-transcriptionally and conform structural scaffoldings binding proteins that control immune cells by modifying their function. Nascent RNA immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs encoding immunomodulatory factors, viral RNA analogues, interference RNAs and protein-binding RNA aptamers. These approaches are already in early clinical development with promising safety and efficacy results.

    更新日期:2018-09-07
  • The hepatocellular carcinoma market
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-31
    Joshua Dawkins, Rachel M. Webster

    The hepatocellular carcinoma marketThe hepatocellular carcinoma market, Published online: 31 August 2018; doi:10.1038/nrd.2018.146The market for hepatocellular carcinoma is set to change with the recent approvals of the kinase inhibitor lenvatinib and the immune checkpoint inhibitor nivolumab, as well as the anticipated approvals of further immunotherapies.

    更新日期:2018-08-31
  • Cancer: Targeting minimal residual disease
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Sarah Crunkhorn

    Cancer: Targeting minimal residual diseaseCancer: Targeting minimal residual disease, Published online: 30 August 2018; doi:10.1038/nrd.2018.141Cancer: Targeting minimal residual disease

    更新日期:2018-08-30
  • Epilepsy: Gene therapy safely reduces seizures in rats
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Sarah Crunkhorn

    Epilepsy: Gene therapy safely reduces seizures in ratsEpilepsy: Gene therapy safely reduces seizures in rats, Published online: 30 August 2018; doi:10.1038/nrd.2018.143Epilepsy: Gene therapy safely reduces seizures in rats

    更新日期:2018-08-30
  • Penny Heaton
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30

    Penny HeatonPenny Heaton, Published online: 30 August 2018; doi:10.1038/nrd.2018.151Penny Heaton, CEO of the Bill and Melinda Gates Medical Research Institute, discusses how the recently launched non-profit biotech will tackle the translational science of TB, malaria and diarrhoeal diseases.

    更新日期:2018-08-30
  • FDA approves second GPCR-targeted antibody
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Asher Mullard

    FDA approves second GPCR-targeted antibodyFDA approves second GPCR-targeted antibody, Published online: 30 August 2018; doi:10.1038/nrd.2018.153FDA approves second GPCR-targeted antibody

    更新日期:2018-08-30
  • Corrigendum: New approaches and challenges to targeting the endocannabinoid system
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Vincenzo Di Marzo

    Corrigendum: New approaches and challenges to targeting the endocannabinoid systemCorrigendum: New approaches and challenges to targeting the endocannabinoid system, Published online: 30 August 2018; doi:10.1038/nrd.2018.155Corrigendum: New approaches and challenges to targeting the endocannabinoid system

    更新日期:2018-08-30
  • Autoimmune disease: Reversing vitiligo
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Sarah Crunkhorn

    Autoimmune disease: Reversing vitiligoAutoimmune disease: Reversing vitiligo, Published online: 30 August 2018; doi:10.1038/nrd.2018.142Autoimmune disease: Reversing vitiligo

    更新日期:2018-08-30
  • Cancer: Overcoming resistance to checkpoint blockade
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Sarah Crunkhorn

    Cancer: Overcoming resistance to checkpoint blockadeCancer: Overcoming resistance to checkpoint blockade, Published online: 30 August 2018; doi:10.1038/nrd.2018.144Cancer: Overcoming resistance to checkpoint blockade

    更新日期:2018-08-30
  • FDA approves landmark RNAi drug
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-30
    Asher Mullard

    FDA approves landmark RNAi drugFDA approves landmark RNAi drug, Published online: 30 August 2018; doi:10.1038/nrd.2018.152FDA approves landmark RNAi drug

    更新日期:2018-08-30
  • Expanding the medicinal chemistry synthetic toolbox
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-24
    Jonas Boström, Dean G. Brown, Robert J. Young, György M. Keserü

    The key objectives of medicinal chemistry are to efficiently design and synthesize bioactive compounds that have the potential to become safe and efficacious drugs. Most medicinal chemistry programmes rely on screening compound collections populated by a range of molecules derived from a set of known and robust chemistry reactions. Analysis of the role of synthetic organic chemistry in subsequent hit and lead optimization efforts suggests that only a few reactions dominate. Thus, the uptake of new synthetic methodologies in drug discovery is limited. Starting from the known limitations of reaction parameters, synthesis design tools, synthetic strategies and innovative chemistries, here we highlight opportunities for the expansion of the medicinal chemists' synthetic toolbox. More intense crosstalk between synthetic and medicinal chemists in industry and academia should enable enhanced impact of new methodologies in future drug discovery.

    更新日期:2018-08-24
  • Spinal cord injury: Ion transporter agonist improves recovery
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Megan Cully

    Spinal cord injury: Ion transporter agonist improves recoverySpinal cord injury: Ion transporter agonist improves recovery, Published online: 17 August 2018; doi:10.1038/nrd.2018.145Spinal cord injury: Ion transporter agonist improves recovery

    更新日期:2018-08-17
  • Targeting the NLRP3 inflammasome in inflammatory diseases
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Matthew S. J. Mangan, Edward J. Olhava, William R. Roush, H. Martin Seidel, Gary D. Glick, Eicke Latz

    Targeting the NLRP3 inflammasome in inflammatory diseasesTargeting the NLRP3 inflammasome in inflammatory diseases, Published online: 17 August 2018; doi:10.1038/nrd.2018.149Targeting the NLRP3 inflammasome in inflammatory diseases

    更新日期:2018-08-17
  • Gene therapy: Gene therapy before the cradle
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    M. Teresa Villanueva

    Gene therapy: Gene therapy before the cradleGene therapy: Gene therapy before the cradle, Published online: 17 August 2018; doi:10.1038/nrd.2018.140Gene therapy: Gene therapy before the cradle

    更新日期:2018-08-17
  • Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Barry Boland, Wai Haung Yu, Olga Corti, Bertrand Mollereau, Alexandre Henriques, Erwan Bezard, Greg M. Pastores, David C. Rubinsztein, Ralph A. Nixon, Michael R. Duchen, Giovanna R. Mallucci, Guido Kroemer, Beth Levine, Eeva-Liisa Eskelinen, Fanny Mochel, Michael Spedding, Caroline Louis, Olivier R. Martin, Mark J. Millan

    Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic–lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin–proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood–brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs.

    更新日期:2018-08-17
  • New approaches and challenges to targeting the endocannabinoid system
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Vincenzo Di Marzo

    The endocannabinoid signalling system was discovered because receptors in this system are the targets of compounds present in psychotropic preparations of Cannabis sativa. The search for new therapeutics that target endocannabinoid signalling is both challenging and potentially rewarding, as endocannabinoids are implicated in numerous physiological and pathological processes. Hundreds of mediators chemically related to the endocannabinoids, often with similar metabolic pathways but different targets, have complicated the development of inhibitors of endocannabinoid metabolic enzymes but have also stimulated the rational design of multi-target drugs. Meanwhile, drugs based on botanical cannabinoids have come to the clinical forefront, synthetic agonists designed to bind cannabinoid receptor 1 with very high affinity have become a societal threat and the gut microbiome has been found to signal in part through the endocannabinoid network. The current development of drugs that alter endocannabinoid signalling and how this complex system could be pharmacologically manipulated in the future are described in this Opinion article.

    更新日期:2018-08-17
  • Pain: Silencing chronic pain with botulinum toxin
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Sarah Crunkhorn

    Pain: Silencing chronic pain with botulinum toxinPain: Silencing chronic pain with botulinum toxin, Published online: 17 August 2018; doi:10.1038/nrd.2018.137Pain: Silencing chronic pain with botulinum toxin

    更新日期:2018-08-17
  • Regenerative medicine: Stem cell-derived cardiomyocytes heal a broken heart
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-17
    Grant Otto

    Regenerative medicine: Stem cell-derived cardiomyocytes heal a broken heartRegenerative medicine: Stem cell-derived cardiomyocytes heal a broken heart, Published online: 17 August 2018; doi:10.1038/nrd.2018.139Regenerative medicine: Stem cell-derived cardiomyocytes heal a broken heart

    更新日期:2018-08-17
  • Gene therapy for neurological disorders: progress and prospects
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-10
    Benjamin E. Deverman, Bernard M. Ravina, Krystof S. Bankiewicz, Steven M. Paul, Dinah W. Y. Sah

    Adeno-associated viral (AAV) vectors are a rapidly emerging gene therapy platform for the treatment of neurological diseases. In preclinical studies, transgenes encoding therapeutic proteins, microRNAs, antibodies or gene-editing machinery have been successfully delivered to the central nervous system with natural or engineered viral capsids via various routes of administration. Importantly, initial clinical studies have demonstrated encouraging safety and efficacy in diseases such as Parkinson disease and spinal muscular atrophy, as well as durability of transgene expression. Here, we discuss key considerations and challenges in the future design and development of therapeutic AAV vectors, highlighting the most promising targets and recent clinical advances.

    更新日期:2018-08-10
  • Anti-ageing pipeline starts to mature
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-08-03
    Asher Mullard

    Anti-ageing pipeline starts to mature Anti-ageing pipeline starts to mature, Published online: 03 August 2018; doi:10.1038/nrd.2018.134 Ongoing and upcoming clinical trials of metformin, mTOR inhibitors and senescent cell-killing drugs could prove that ageing and ageing-related diseases are viable drug discovery indications.

    更新日期:2018-08-03
  • A snapshot of lead-generation strategies
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Asher Mullard

    A snapshot of lead-generation strategies A snapshot of lead-generation strategies, Published online: 30 July 2018; doi:10.1038/nrd.2018.129 A snapshot of lead-generation strategies

    更新日期:2018-07-30
  • Metabolic disorders: IDO inhibitors could change tack to treat metabolic disorders
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Megan Cully

    Metabolic disorders: IDO inhibitors could change tack to treat metabolic disorders Metabolic disorders: IDO inhibitors could change tack to treat metabolic disorders, Published online: 30 July 2018; doi:10.1038/nrd.2018.124 Metabolic disorders: IDO inhibitors could change tack to treat metabolic disorders

    更新日期:2018-07-30
  • Regulatory watch: FDA new drug approvals in Q2 2018
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Lisa Urquhart

    Regulatory watch: FDA new drug approvals in Q2 2018 Regulatory watch: FDA new drug approvals in Q2 2018, Published online: 30 July 2018; doi:10.1038/nrd.2018.126 Regulatory watch: FDA new drug approvals in Q2 2018

    更新日期:2018-07-30
  • REVAMPing antibiotic incentives
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Asher Mullard

    REVAMPing antibiotic incentives REVAMPing antibiotic incentives, Published online: 30 July 2018; doi:10.1038/nrd.2018.130 REVAMPing antibiotic incentives

    更新日期:2018-07-30
  • Constrained peptides' time to shine?
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Chris Morrison

    Constrained peptides' time to shine? Constrained peptides' time to shine?, Published online: 30 July 2018; doi:10.1038/nrd.2018.125 Constrained peptides have long tantalized drug developers with their potential ability to combine the best attributes of antibodies and small molecules. Finally, a handful of constrained peptides are in late-stage clinical trials.

    更新日期:2018-07-30
  • Saurabh Saha
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30

    Saurabh Saha Saurabh Saha, Published online: 30 July 2018; doi:10.1038/nrd.2018.127 Saurabh Saha, head of Translational Medicine at Bristol-Myers Squibb, discusses how new tools are opening up translational opportunities in immuno-oncology

    更新日期:2018-07-30
  • FDA approves first marijuana-derived product
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-30
    Asher Mullard

    FDA approves first marijuana-derived product FDA approves first marijuana-derived product, Published online: 30 July 2018; doi:10.1038/nrd.2018.131 FDA approves first marijuana-derived product

    更新日期:2018-07-30
  • Genetic disorders: PI3K inhibitor reverses overgrowth syndrome
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Sarah Crunkhorn

    Genetic disorders: PI3K inhibitor reverses overgrowth syndrome Genetic disorders: PI3K inhibitor reverses overgrowth syndrome, Published online: 20 July 2018; doi:10.1038/nrd.2018.120 Genetic disorders: PI3K inhibitor reverses overgrowth syndrome

    更新日期:2018-07-21
  • Cancer: Releasing tumour suppressors
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Sarah Crunkhorn

    Cancer: Releasing tumour suppressors Cancer: Releasing tumour suppressors, Published online: 20 July 2018; doi:10.1038/nrd.2018.118 Cancer: Releasing tumour suppressors

    更新日期:2018-07-21
  • Autoimmune disease: A human antibody selectively targets regulatory T cells
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Grant Otto

    Autoimmune disease: A human antibody selectively targets regulatory T cells Autoimmune disease: A human antibody selectively targets regulatory T cells, Published online: 20 July 2018; doi:10.1038/nrd.2018.122 Autoimmune disease: A human antibody selectively targets regulatory T cells

    更新日期:2018-07-21
  • Trends driving clinical trials into large clinical care settings
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Kenneth Getz

    Trends driving clinical trials into large clinical care settings Trends driving clinical trials into large clinical care settings, Published online: 20 July 2018; doi:10.1038/nrd.2018.111 This analysis highlights data indicating the limitations of traditional clinical trial processes, and discusses how moving clinical trials into large clinical care settings could help meet the growing demands for large volumes of sophisticated patient data.

    更新日期:2018-07-21
  • Targeting the NLRP3 inflammasome in inflammatory diseases
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Matthew S. J. Mangan, Edward J. Olhava, William R. Roush, H. Martin Seidel, Gary D. Glick, Eicke Latz

    Danger signals are a hallmark of many common inflammatory diseases, and these stimuli can function to activate the cytosolic innate immune signalling receptor NLRP3 (NOD-, LRR- and pyrin domain-containing 3). Once activated, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Pharmacological inhibition of NLRP3 activation results in potent therapeutic effects in a wide variety of rodent models of inflammatory diseases, effects that are mirrored by genetic ablation of NLRP3. Although these findings highlight the potential of NLRP3 as a drug target, an understanding of NLRP3 structure and activation mechanisms is incomplete, which has hampered the discovery and development of novel therapeutics against this target. Here, we review recent advances in our understanding of NLRP3 activation and regulation, highlight the evolving landscape of NLRP3 modulators and discuss opportunities for pharmacologically targeting NLRP3 with novel small molecules.

    更新日期:2018-07-21
  • Cardiovascular disease: Improving cardiomyocyte contractility
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Sarah Crunkhorn

    Cardiovascular disease: Improving cardiomyocyte contractility Cardiovascular disease: Improving cardiomyocyte contractility, Published online: 20 July 2018; doi:10.1038/nrd.2018.117 Cardiovascular disease: Improving cardiomyocyte contractility

    更新日期:2018-07-21
  • Infectious disease: Curbing cholera
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    Sarah Crunkhorn

    Infectious disease: Curbing cholera Infectious disease: Curbing cholera, Published online: 20 July 2018; doi:10.1038/nrd.2018.119 Infectious disease: Curbing cholera

    更新日期:2018-07-21
  • Anticancer therapy: Metabolic synthetic lethality
    Nat. Rev. Drug. Disc. (IF 50.167) Pub Date : 2018-07-20
    M. Teresa Villanueva

    Anticancer therapy: Metabolic synthetic lethality Anticancer therapy: Metabolic synthetic lethality, Published online: 20 July 2018; doi:10.1038/nrd.2018.123 Anticancer therapy: Metabolic synthetic lethality

    更新日期:2018-07-21
  • 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
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.
化学 • 材料 期刊列表