3,141 results match your criteria Nature Reviews Drug Discovery[Journal]


Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond.

Nat Rev Drug Discov 2019 Feb 13. Epub 2019 Feb 13.

DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), INF 280, Heidelberg, Germany.

L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative. Read More

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http://dx.doi.org/10.1038/s41573-019-0016-5DOI Listing
February 2019

Antibodies and venom peptides: new modalities for ion channels.

Nat Rev Drug Discov 2019 Feb 6. Epub 2019 Feb 6.

Department of Physiology & Membrane Biology, University of California Davis, Davis, CA, USA.

Ion channels play fundamental roles in both excitable and non-excitable tissues and therefore constitute attractive drug targets for myriad neurological, cardiovascular and metabolic diseases as well as for cancer and immunomodulation. However, achieving selectivity for specific ion channel subtypes with small-molecule drugs has been challenging, and there currently is a growing trend to target ion channels with biologics. One approach is to improve the pharmacokinetics of existing or novel venom-derived peptides. Read More

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http://www.nature.com/articles/s41573-019-0013-8
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http://dx.doi.org/10.1038/s41573-019-0013-8DOI Listing
February 2019
7 Reads

2018 FDA drug approvals.

Authors:
Asher Mullard

Nat Rev Drug Discov 2019 Feb;18(2):85-89

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http://dx.doi.org/10.1038/d41573-019-00014-xDOI Listing
February 2019
1 Read

2018 FDA approvals hit all time high - but average value slips again.

Nat Rev Drug Discov 2019 Feb;18(2):90

Boston Consulting Group, Boston, Zürich, Switzerland.

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http://www.nature.com/articles/d41573-019-00004-z
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http://dx.doi.org/10.1038/d41573-019-00004-zDOI Listing
February 2019
3 Reads

Biopharma dealmaking in 2018.

Nat Rev Drug Discov 2019 Feb;18(2):93-94

Informa, 52 Vanderbilt Avenue, New York, New York, 10017, USA.

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http://www.nature.com/articles/d41573-019-00013-y
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http://dx.doi.org/10.1038/d41573-019-00013-yDOI Listing
February 2019
2 Reads

Developing closed-loop neuromodulatory devices.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2019 Feb;18(2):98

Nature Reviews Drug Discovery, .

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http://www.nature.com/articles/d41573-019-00011-0
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http://dx.doi.org/10.1038/d41573-019-00011-0DOI Listing
February 2019
3 Reads

Role of the Protein Data Bank.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2019 Feb;18(2):98

Nature Reviews Drug Discovery, .

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http://www.nature.com/articles/d41573-019-00010-1
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http://dx.doi.org/10.1038/d41573-019-00010-1DOI Listing
February 2019
3 Reads

Top product forecasts for 2019.

Authors:
Lisa Urquhart

Nat Rev Drug Discov 2019 Feb;18(2):91

Vantage, London, UK.

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http://dx.doi.org/10.1038/d41573-019-00012-zDOI Listing
February 2019

Identifying antimalarial drug targets.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2019 Feb;18(2):98

Nature Reviews Drug Discovery, .

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http://dx.doi.org/10.1038/d41573-019-00009-8DOI Listing
February 2019
3 Reads

Novel incretin receptor antibodies combat weight gain.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2019 Feb;18(2):95

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http://dx.doi.org/10.1038/d41573-019-00008-9DOI Listing
February 2019
2 Reads

An exercise-linked mediator of memory protection.

Authors:
Katie Kingwell

Nat Rev Drug Discov 2019 Feb;18(2):97

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http://www.nature.com/articles/d41573-019-00006-x
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http://dx.doi.org/10.1038/d41573-019-00006-xDOI Listing
February 2019
1 Read

Mapping biologically active chemical space to accelerate drug discovery.

Nat Rev Drug Discov 2019 Feb;18(2):83-84

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1038/d41573-018-00007-2DOI Listing
February 2019

Unmasking cancer cell character.

Nat Rev Drug Discov 2019 Feb;18(2):96

Nature Reviews Drug Discovery, .

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http://dx.doi.org/10.1038/d41573-019-00005-yDOI Listing
February 2019
3 Reads

GABA receptor structures solved.

Authors:
Megan Cully

Nat Rev Drug Discov 2019 Feb;18(2):98

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http://dx.doi.org/10.1038/d41573-019-00002-1DOI Listing
February 2019
3 Reads

Adeno-associated virus vector as a platform for gene therapy delivery.

Nat Rev Drug Discov 2019 Feb 1. Epub 2019 Feb 1.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.

Adeno-associated virus (AAV) vectors are the leading platform for gene delivery for the treatment of a variety of human diseases. Recent advances in developing clinically desirable AAV capsids, optimizing genome designs and harnessing revolutionary biotechnologies have contributed substantially to the growth of the gene therapy field. Preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene editing have helped AAV gain popularity as the ideal therapeutic vector, with two AAV-based therapeutics gaining regulatory approval in Europe or the United States. Read More

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http://dx.doi.org/10.1038/s41573-019-0012-9DOI Listing
February 2019
13 Reads

Interferons α and β in cancer: therapeutic opportunities from new insights.

Authors:
Ernest C Borden

Nat Rev Drug Discov 2019 Jan 24. Epub 2019 Jan 24.

Department of Human Oncology, University of Wiconsin Carbone Cancer Center, Madison, WI, USA.

Over the past decade, preclinical and clinical research have confirmed the essential role of interferons for effective host immunological responses to malignant cells. Type I interferons (IFNα and IFNβ) directly regulate transcription of >100 downstream genes, which results in a myriad of direct (on cancer cells) and indirect (through immune effector cells and vasculature) effects on the tumour. New insights into endogenous and exogenous activation of type I interferons in the tumour and its microenvironment have given impetus to drug discovery and patient evaluation of interferon-directed strategies. Read More

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http://www.nature.com/articles/s41573-018-0011-2
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http://dx.doi.org/10.1038/s41573-018-0011-2DOI Listing
January 2019
5 Reads

The virtuous cycle of human genetics and mouse models in drug discovery.

Nat Rev Drug Discov 2019 Jan 24. Epub 2019 Jan 24.

Laboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Ongoing studies in many species seek to understand the origins, architecture and consequences of phenotypic variation under normal and dysfunctional conditions, with the aim of identifying targets for intervention that can prevent, stabilize or reverse disease. Some suggest that only humans are appropriate for studying these questions and argue that candidate drug targets identified in mouse models are largely unreliable. Here, we review the vast evidence showing that mouse models continue to make fundamental contributions to our understanding of genetic principles, pathogenic mechanisms and therapeutic modalities. Read More

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http://www.nature.com/articles/s41573-018-0009-9
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http://dx.doi.org/10.1038/s41573-018-0009-9DOI Listing
January 2019
5 Reads

Delivery technologies for cancer immunotherapy.

Nat Rev Drug Discov 2019 Jan 8. Epub 2019 Jan 8.

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.

Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Read More

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http://dx.doi.org/10.1038/s41573-018-0006-zDOI Listing
January 2019
30 Reads

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies.

Nat Rev Drug Discov 2019 Jan 4. Epub 2019 Jan 4.

INSERM, Laboratory of Integrative Cancer Immunology, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Centre de Recherche des Cordeliers, Paris, France.

Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Read More

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http://www.nature.com/articles/s41573-018-0007-y
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http://dx.doi.org/10.1038/s41573-018-0007-yDOI Listing
January 2019
3 Reads

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.

Nat Rev Drug Discov 2019 Jan 4. Epub 2019 Jan 4.

Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, Scotland, UK.

The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. Read More

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http://dx.doi.org/10.1038/s41573-018-0008-xDOI Listing
January 2019
2 Reads

Anticancer drugs: Cutting down on prostate cancer metastases.

Authors:
Megan Cully

Nat Rev Drug Discov 2018 Dec;18(1):17

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http://dx.doi.org/10.1038/nrd.2018.225DOI Listing
December 2018
1 Read

Cancer immunotherapy: STINGing systemically.

Nat Rev Drug Discov 2018 Dec;18(1):15

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http://dx.doi.org/10.1038/nrd.2018.236DOI Listing
December 2018

Drug discovery: Targeting transcription factors.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Dec;18(1):18

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http://dx.doi.org/10.1038/nrd.2018.231DOI Listing
December 2018
1 Read

RNA interference: Pre-empting preeclampsia.

Authors:
Katie Kingwell

Nat Rev Drug Discov 2018 Dec;18(1):18

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http://dx.doi.org/10.1038/nrd.2018.235DOI Listing
December 2018
1 Read

Low-cost non-profit drug repurposing.

Authors:
Asher Mullard

Nat Rev Drug Discov 2018 Dec;18(1)

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http://dx.doi.org/10.1038/nrd.2018.228DOI Listing
December 2018
1 Read

Cancer: Repurposing SGLT2 inhibitors.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Dec;18(1):18

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http://dx.doi.org/10.1038/nrd.2018.229DOI Listing
December 2018
1 Read

Peanut allergy potential.

Authors:
Asher Mullard

Nat Rev Drug Discov 2018 Dec;18(1)

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http://dx.doi.org/10.1038/nrd.2018.227DOI Listing
December 2018
1 Read

Boom: 2018's biotech IPOs.

Authors:
Chris Morrison

Nat Rev Drug Discov 2018 Dec;18(1):3-6

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http://dx.doi.org/10.1038/nrd.2018.233DOI Listing
December 2018
1 Read

Obesity: Role of BAT in satiation.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Dec;18(1):18

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http://dx.doi.org/10.1038/nrd.2018.230DOI Listing
December 2018

FDA approves landmark tissue-agnostic cancer drug.

Authors:
Asher Mullard

Nat Rev Drug Discov 2018 Dec;18(1)

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http://dx.doi.org/10.1038/nrd.2018.226DOI Listing
December 2018
1 Read

Market watch: Upcoming market catalysts in Q1 2019.

Authors:
Khang Hoang

Nat Rev Drug Discov 2018 Dec;18(1)

Sagient Research Systems, an Informa business, San Diego, CA, USA.

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http://dx.doi.org/10.1038/nrd.2018.223DOI Listing
December 2018
1 Read

Cancer: Combating resistance to EGFR inhibitors.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Dec;18(1):18

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http://dx.doi.org/10.1038/nrd.2018.232DOI Listing
December 2018
1 Read

Inflammatory disorders: Blocking proinflammatory gene transcription.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Dec;18(1):16

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http://dx.doi.org/10.1038/nrd.2018.224DOI Listing
December 2018
1 Read

Rick Brown.

Authors:

Nat Rev Drug Discov 2018 Dec;18(1):10-11

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http://dx.doi.org/10.1038/nrd.2018.237DOI Listing
December 2018

The implications of target saturation for the use of drug-target residence time.

Nat Rev Drug Discov 2018 Dec;18(1):82-84

Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.

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http://dx.doi.org/10.1038/nrd.2018.234DOI Listing
December 2018
1 Read

Polymer-drug conjugate therapeutics: advances, insights and prospects.

Nat Rev Drug Discov 2018 Dec 12. Epub 2018 Dec 12.

Departments of Biomedical Engineering, Chemistry, and Medicine, Boston University, Boston, MA, USA.

Polymer-drug conjugates have long been a mainstay of the drug delivery field, with several conjugates successfully translated into clinical practice. The conjugation of therapeutic agents to polymeric carriers, such as polyethylene glycol, offers several advantages, including improved drug solubilization, prolonged circulation, reduced immunogenicity, controlled release and enhanced safety. In this Review, we discuss the rational design, physicochemical characteristics and recent advances in the development of different classes of polymer-drug conjugates, including polymer-protein and polymer-small-molecule drug conjugates, dendrimers, polymer nanoparticles and multifunctional systems. Read More

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http://dx.doi.org/10.1038/s41573-018-0005-0DOI Listing
December 2018
2 Reads

Therapeutic potential of ectopic olfactory and taste receptors.

Nat Rev Drug Discov 2019 Feb;18(2):116-138

Faculty of Biology & Biotechnology, Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.

Olfactory and taste receptors are expressed primarily in the nasal olfactory epithelium and gustatory taste bud cells, where they transmit real-time sensory signals to the brain. However, they are also expressed in multiple extra-nasal and extra-oral tissues, being implicated in diverse biological processes including sperm chemotaxis, muscle regeneration, bronchoconstriction and bronchodilatation, inflammation, appetite regulation and energy metabolism. Elucidation of the physiological roles of these ectopic receptors is revealing potential therapeutic and diagnostic applications in conditions including wounds, hair loss, asthma, obesity and cancers. Read More

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http://dx.doi.org/10.1038/s41573-018-0002-3DOI Listing
February 2019
2 Reads

Therapeutic strategies for sickle cell disease: towards a multi-agent approach.

Nat Rev Drug Discov 2019 Feb;18(2):139-158

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlusion, anaemia, haemolysis, organ injury and pain. However, despite growing understanding of the mechanisms of haemoglobin S polymerization and its effects on red blood cells, only two therapies for SCD - hydroxyurea and L-glutamine - are approved by the US Food and Drug Administration. Moreover, these treatment options do not fully address the manifestations of SCD, which arise from a complex network of interdependent pathophysiological processes. Read More

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http://www.nature.com/articles/s41573-018-0003-2
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http://dx.doi.org/10.1038/s41573-018-0003-2DOI Listing
February 2019
15 Reads

Regulatory watch: European regulatory experience with advanced therapy medicinal products.

Nat Rev Drug Discov 2018 Nov 30. Epub 2018 Nov 30.

Paul-Ehrlich-Institut, Langen, Germany.

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http://dx.doi.org/10.1038/nrd.2018.200DOI Listing
November 2018
1 Read

Non-invasive delivery strategies for biologics.

Nat Rev Drug Discov 2018 Nov 30. Epub 2018 Nov 30.

John A. Paulson School of Engineering and Applied Sciences, Wyss Institute of Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.

Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Read More

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http://www.nature.com/doifinder/10.1038/nrd.2018.183
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http://dx.doi.org/10.1038/nrd.2018.183DOI Listing
November 2018
12 Reads

Antifungal drugs: Small molecules targeting a tertiary RNA structure fight fungi.

Authors:
Megan Cully

Nat Rev Drug Discov 2018 Nov;17(12):864

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http://dx.doi.org/10.1038/nrd.2018.205DOI Listing
November 2018
1 Read

Type 2 diabetes: Microbial metabolite impairs insulin signaling.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Nov;17(12):864

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http://dx.doi.org/10.1038/nrd.2018.215DOI Listing
November 2018
1 Read

FDA approves first new flu drug in 20 years.

Authors:
Asher Mullard

Nat Rev Drug Discov 2018 Nov;17(12):853

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http://dx.doi.org/10.1038/nrd.2018.219DOI Listing
November 2018
1 Read

Samantha Du.

Authors:

Nat Rev Drug Discov 2018 Nov;17(12):856-857

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http://dx.doi.org/10.1038/nrd.2018.208DOI Listing
November 2018
1 Read

Anticancer drugs: Translational target for checkpoint inhibitors.

Authors:
Katie Kingwell

Nat Rev Drug Discov 2018 Nov;17(12):863

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http://dx.doi.org/10.1038/nrd.2018.204DOI Listing
November 2018
1 Read

Drug repurposing: Heart failure drug effective in medulloblastoma.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Nov;17(12):864

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http://dx.doi.org/10.1038/nrd.2018.213DOI Listing
November 2018
2 Reads

Aging: Promoting NAD production.

Authors:
Sarah Crunkhorn

Nat Rev Drug Discov 2018 Nov;17(12):864

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http://dx.doi.org/10.1038/nrd.2018.212DOI Listing
November 2018
1 Read

Anti-inflammatory cardiovascular therapies take another hit.

Authors:
Asher Mullard

Nat Rev Drug Discov 2018 Nov;17(12):853

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http://dx.doi.org/10.1038/nrd.2018.218DOI Listing
November 2018
1 Read