Antibiotics: Reversing resistance
Nature Reviews Drug Discovery 16, 314 (2017). doi:10.1038/nrd.2017.74 Author: Crunkhorn Sarah Acquired Mycobacterium tuberculosis resistance to the commonly used antibiotic ethionamide (ETH) is mediated by mutations in the bacterial enzymatic pathway that is required for biological activation of the drug. Here, Blondiaux et al. identify a series of spiroisoxazoline compounds — named small molecules (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: CrunkhornSarah Tags: Research Highlight Source Type: research

Analgesia: Designing out opioid side effects
Nature Reviews Drug Discovery 16, 311 (2017). doi:10.1038/nrd.2017.68 Author: M. Teresa Villanueva Although opioids are very effective in treating pain that is associated with tissue damage and inflammation, they have important adverse effects, such as drowsiness, constipation, potential respiratory arrest and addiction. By analysing drug–opioid receptor interactions in damaged tissues, as opposed to healthy tissues, Stein and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Trial watch: Trends in clinical trial design complexity
Nature Reviews Drug Discovery 16, 307 (2017). doi:10.1038/nrd.2017.65 Authors: Kenneth A. Getz & Rafael A. Campo The challenges of measuring the safety and efficacy of investigational drugs that target chronic, difficult-to-treat or rare diseases in more narrowly defined patient subpopulations have increased the scope of clinical trials and the burden to execute them in the past 15 years. Other factors affecting (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: Kenneth A. Getz Rafael A. Campo Tags: News and Analysis Source Type: research

An audience with Jay Bradner
Nature Reviews Drug Discovery 16, 367 (2017). doi:10.1038/nrd.2017.71 Author: Asher Mullard Nature Reviews Drug Discovery16, 232–233 (2017)Two typographical errors that may have affected the meaning of the answers related to the creation of the Chemical Biology & Therapeutics unit within NIBR and the focus of the NIBR leadership (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: Erratum Source Type: research

G protein-coupled receptors: Novel probe for MRGPRX2
Nature Reviews Drug Discovery 16, 314 (2017). doi:10.1038/nrd.2017.77 Author: Crunkhorn Sarah The orphan MAS-related G protein-coupled receptor member X2 (MRGPRX2) is expressed primarily in human dorsal root ganglia and mast cells, and has been suggested to modulate pain and itch. Using a high-throughput screen of 5,695 unique compounds, Lansu et al. discovered that many exogenous (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: CrunkhornSarah Tags: Research Highlight Source Type: research

Cancer: Identifying synergistic drug combinations
Nature Reviews Drug Discovery 16, 314 (2017). doi:10.1038/nrd.2017.76 Author: Crunkhorn Sarah Drug combinations are commonly used to counter drug resistance in cancer therapy. To identify synergistic drug target combinations, Han et al. have developed a scalable CRISPR-based double-knockout system that enables parallel pairwise gene knockout. Application of this system in a chronic myeloid leukaemia (CML) (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: CrunkhornSarah Tags: Research Highlight Source Type: research

Viral infections: Targeting host kinases
Nature Reviews Drug Discovery 16, 314 (2017). doi:10.1038/nrd.2017.75 Author: Crunkhorn Sarah Targeting host pathways that are exploited by viruses represents a promising antiviral strategy. Bekerman et al. show that the host cell kinases AP2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK), which activate the host adapter proteins AP1 and AP2, are required by (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: CrunkhornSarah Tags: Research Highlight Source Type: research

Antibiotics: Reversing resistance
Nature Reviews Drug Discovery 16, 314 (2017). doi:10.1038/nrd.2017.74 Author: Crunkhorn Sarah Acquired Mycobacterium tuberculosis resistance to the commonly used antibiotic ethionamide (ETH) is mediated by mutations in the bacterial enzymatic pathway that is required for biological activation of the drug. Here, Blondiaux et al. identify a series of spiroisoxazoline compounds — named small molecules (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: CrunkhornSarah Tags: Research Highlight Source Type: research

Analgesia: Designing out opioid side effects
Nature Reviews Drug Discovery 16, 311 (2017). doi:10.1038/nrd.2017.68 Author: M. Teresa Villanueva Although opioids are very effective in treating pain that is associated with tissue damage and inflammation, they have important adverse effects, such as drowsiness, constipation, potential respiratory arrest and addiction. By analysing drug–opioid receptor interactions in damaged tissues, as opposed to healthy tissues, Stein and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Trial watch: Trends in clinical trial design complexity
Nature Reviews Drug Discovery 16, 307 (2017). doi:10.1038/nrd.2017.65 Authors: Kenneth A. Getz & Rafael A. Campo The challenges of measuring the safety and efficacy of investigational drugs that target chronic, difficult-to-treat or rare diseases in more narrowly defined patient subpopulations have increased the scope of clinical trials and the burden to execute them in the past 15 years. Other factors affecting (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 18, 2017 Category: Drugs & Pharmacology Authors: Kenneth A. Getz Rafael A. Campo Tags: News and Analysis Source Type: research

Bracing for the biosimilar wave
Nature Reviews Drug Discovery 16, 367 (2017). doi:10.1038/nrd.2017.64 Author: Asher Mullard Nature Reviews Drug Discovery16, 152–154 (2017)The article has been updated to indicate that Sandoz ran a confirmatory study in chronic plaque psoriasis of its etanercept biosimilar versus active comparator, rather than versus placebo. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 31, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: Corrigendum Source Type: research

Cancer: Bacterium-based immunotherapy
Nature Reviews Drug Discovery 16, 240 (2017). doi:10.1038/nrd.2017.54 Author: Sarah Crunkhorn Anaerobic bacteria can accumulate and proliferate within hypoxic and necrotic regions of solid tumours, stimulating inflammation and triggering an antitumour immune response. Zheng et al. have engineered an attenuated strain of Salmonella typhimurium to overexpress and secrete a heterologous bacterial flagellin (FlaB), which (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cardiovascular disease: Thioredoxin lowers hypertension
Nature Reviews Drug Discovery 16, 240 (2017). doi:10.1038/nrd.2017.53 Author: Sarah Crunkhorn The development of long-lasting antihypertensive therapies represents a crucial unmet need. Hilgers et al. now report that mice overexpressing the redox protein thioredoxin (TRX) are protected from age-related hypertension. Furthermore, injection of aged mice with recombinant human TRX (rhTRX) lowered blood pressure to levels (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Drug toxicity: Cardiac safety index for TKIs
Nature Reviews Drug Discovery 16, 240 (2017). doi:10.1038/nrd.2017.52 Author: Sarah Crunkhorn Tyrosine kinase inhibitors (TKIs) represent efficacious anticancer agents, but their use has been linked with severe cardiotoxicity. Here, Sharma et al. generated human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, hiPSC-derived endothelial cells and hiPSC-derived cardiac fibroblasts to evaluate the cardiotoxicities of 21 US FDA-approved (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research