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2017 FDA drug approvals
Nature Reviews Drug Discovery 17, 150 (2018). doi:10.1038/nrd.2018.18 Author: Asher Mullard Nature Reviews Drug Discovery17, 81–85 (2018)Semaglutide is the sixth GLP1 agonist to receive FDA approval, not the fifth as originally noted. This correction has been made in the print and online versions. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: Corrigendum Source Type: research

Inflammation: Microbiome manipulation ameliorates colitis
Nature Reviews Drug Discovery 17, 96 (2018). doi:10.1038/nrd.2018.9 Author: Sarah Crunkhorn Intestinal inflammation and gut microbiota dysbiosis are closely associated. Using mouse models of colitis, Zhu et al. demonstrate that administration of sodium tungstate in drinking water selectively controls the expansion of bacterial populations, such as Enterobacteriaceae, that rely on molybdenum cofactor-dependent processes, shifting the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Neurodegenerative diseases: Inflammasome protein seeds plaques in Alzheimer disease
Nature Reviews Drug Discovery 17, 96 (2018). doi:10.1038/nrd.2018.5 Author: Megan Cully Alzheimer disease is characterized by the presence of amyloid-β (Aβ) plaques in the brain (which are thought to cause neuronal dysfunction), as well as by neurochemical changes and inflammation. Writing in Nature, Venegas and colleagues found that aggregates of apoptosis-associated speck-like protein containing a (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research

Immunotherapy: Oncolytic virotherapy enables checkpoint blockade
Nature Reviews Drug Discovery 17, 96 (2018). doi:10.1038/nrd.2018.11 Author: Sarah Crunkhorn Immune checkpoint inhibitors have yielded promising results in various cancer types, but are only effective in a subset of cancer patients, particularly those exhibiting pre-existing anticancer immunity. Two new papers now report the use of an oncolytic virus (OV) to induce antitumour immunity and increase (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer: Anticancer effects of alcohol abuse drug
Nature Reviews Drug Discovery 17, 96 (2018). doi:10.1038/nrd.2018.10 Author: Sarah Crunkhorn Although the alcohol-aversion drug disulfiram (DSF) is effective against diverse cancer types in preclinical models, its mechanism of action remains unknown. Here, Skrott et al. analysed the Danish nationwide demographic and health registries, which revealed a reduced cancer-specific mortality when the use of DSF (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Gene therapy: CRISPR therapies — making the grade not the cut
Nature Reviews Drug Discovery 17, 95 (2018). doi:10.1038/nrd.2018.3 Author: Darren J. Burgess CRISPR-based systems for therapeutic purposes have shown promise in numerous mouse models of human diseases, but one concern that is limiting roll-out to human trials is that during genome editing, unintended Cas9-induced DNA double-strand breaks (DSBs) could cause off-target mutations, toxicity and harm to patients. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Darren J. Burgess Tags: Research Highlight Source Type: research

Pharmacogenomics: Know your GPCR mutations (and target them right)
Nature Reviews Drug Discovery 17, 94 (2018). doi:10.1038/nrd.2018.13 Author: M. Teresa Villanueva Natural human genetic variations may cause patients to respond differently to the same medication. Therefore, understanding genetic variation in drug targets can maximize efficacy and reduce side effects. In a new study, a team led by M. Madan Babu present a comprehensive analysis of G (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Regenerative medicine: Cholesterol clearance restores remyelination
Nature Reviews Drug Discovery 17, 94 (2018). doi:10.1038/nrd.2018.12 Author: Katie Kingwell In progressive demyelinating diseases such as multiple sclerosis, the capacity to repair myelin damage declines with age, which limits functional recovery. Reporting in Science, Simons and colleagues have pinpointed overload of the cholesterol clearance machinery in central nervous system (CNS) macrophages as a key (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Katie Kingwell Tags: Research Highlight Source Type: research

Gene therapy: Reprogramming α -cells reverses diabetes
Nature Reviews Drug Discovery 17, 93 (2018). doi:10.1038/nrd.2018.7 Author: Sarah Crunkhorn Autoimmune destruction of insulin (INS)-producing pancreatic β-cells, resulting in persistent hyperglycaemia, underlies the pathogenesis of type 1 diabetes. Preserving and restoring functional β-cell mass is therefore a fundamental objective of diabetes therapy. Writing in Cell Stem Cell, Gittes and colleagues report the successful conversion (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Biopharma deal-making in 2017
This article analyses merger and acquisition (M&A) activity and partnerships in the biopharma industry in 2017, highlighting trends and major deals. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Amanda Micklus Steven Muntner Tags: News and Analysis Source Type: research

EMA recommended 35 new drugs in 2017
Nature Reviews Drug Discovery 17, 86 (2018). doi:10.1038/nrd.2018.17 Author: Asher Mullard The European Medicines Agency (EMA) recommended approval for 35 new therapeutic agents last year, compared with 27 in 2016 and 39 in 2015.The EMA's count includes small molecules, antibodies, biologics, blood products, cellular therapies and vaccines. As such, it cannot be compared directly (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Pfizer exits neuroscience
Nature Reviews Drug Discovery 17, 86 (2018). doi:10.1038/nrd.2018.16 Author: Asher Mullard Pfizer is pulling out of neuroscience drug discovery and early development, and cutting 300 positions in its neuroscience division.Prior to the announcement, the company had eight neuroscience products in phase I and phase II trials. These consisted of four clinical programmes in Alzheimer disease, (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Top product sales forecasts for 2018
Nature Reviews Drug Discovery 17, 86 (2018). doi:10.1038/nrd.2018.15 Author: Asher Mullard The top-selling drugs of 2018 are set to be a mix of old-timers and newcomers, shows global consensus sales forecast data from EvaluatePharma.The top five products on this forecast list are repeat bestsellers, and AbbVie's adalimumab held the top slot in both 2016 and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 1, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Morgan Sheng
Nature Reviews Drug Discovery 17, 88 (2018). doi:10.1038/nrd.2017.271 In 2006, Genentech re-entered into the neuroscience fray by partnering with AC Immune to develop novel Alzheimer disease treatments. A year and half later, Morgan Sheng joined the biotech firm as Vice President of Neuroscience, and was tasked with putting together a plan to eke new drug candidates out of emerging science. Ten years on, the firm's neuroscience pipeline includes three Alzheimer drugs, one amyotrophic lateral sclerosis drug, one pain drug and a number of preclinical candidates. Sheng spoke with Asher Mullard about his continued faith i...
Source: Nature Reviews Drug Discovery - January 19, 2018 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Market watch: 2017 FDA drug approvals: number rebounds but average value slips
Nature Reviews Drug Discovery 17, 87 (2018). doi:10.1038/nrd.2018.2 Authors: Mathias Baedeker, Michael Ringel, Valery Panier & Ulrik Schulze In line with our outlook last year (Nat Rev. Drug Discov.16, 78; 2017), there was a rebound in the number of new drugs approved by the FDA in 2017 compared with 2016 (Nat. Rev. Drug Discov. 17, 81–85; (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - January 19, 2018 Category: Drugs & Pharmacology Authors: Mathias Baedeker Michael Ringel Valery Panier Ulrik Schulze Tags: News and Analysis Source Type: research

2017 FDA drug approvals
Nature Reviews Drug Discovery 17, 81 (2018). doi:10.1038/nrd.2018.4 Author: Asher Mullard The FDA approved 46 new drugs last year, the highest total in more than two decades. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - January 19, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Market watch: Upcoming market catalysts in Q1 2018
Nature Reviews Drug Discovery 17, 8 (2018). doi:10.1038/nrd.2017.263 Author: Tanner Collins Potential market catalysts in the first quarter of 2018 include important top-line clinical trial results for rigerimod (developed by ImmuPharma and SymBio) for systemic lupus erythematosus (SLE); ofranergene obadenovec (developed by VBL Therapeutics and NanoCarrier) for recurrent glioblastoma (rGBM); and azeliragon (developed by vTv Therapeutics) (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Tanner Collins Tags: News and Analysis Source Type: research

Can innate immune system targets turn up the heat on 'cold' tumours?
Nature Reviews Drug Discovery 17, 3 (2018). doi:10.1038/nrd.2017.264 Author: Asher Mullard STING, RIG-I and NLRP3 agonists might increase the effectiveness of immuno-oncology checkpoint inhibitors, while antagonists of these targets offer an anti-inflammatory bonus. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

JAK inhibition as a therapeutic strategy for immune and inflammatory diseases
Nature Reviews Drug Discovery 17, 78 (2018). doi:10.1038/nrd.2017.267 Author: Daniella M. Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina & John J. O'Shea Nature Reviews Drug Discovery16, 843–862 (2017)In the version of this article that was originally published, there was an error in Figure 3 on page 847. In this figure, the structure attributed to the compound BMS-986165 is (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Daniella M. Schwartz Yuka Kanno Alejandro Villarino Michael Ward Massimo Gadina John J. O'Shea Tags: Corrigendum Source Type: research

Cancer: Inhibiting DNA damage signalling
Nature Reviews Drug Discovery 17, 18 (2018). doi:10.1038/nrd.2017.261 Author: Sarah Crunkhorn The DNA transposase, piggyBac transposable element-derived 5 (PGBD5), is expressed in the majority of childhood solid tumours, where it promotes site-specific genomic rearrangements. Henssen et al. hypothesized that PGBD5-expressing cells may depend on active DNA damage repair and signalling for survival. Indeed, cell lines (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Technology: New method for endogenous protein degradation
Nature Reviews Drug Discovery 17, 18 (2018). doi:10.1038/nrd.2017.260 Author: Sarah Crunkhorn Current strategies to modulate protein expression rely on DNA knock out or RNA interference. A novel method — Trim-Away — can directly and rapidly degrade endogenous proteins in mammalian cells, minimizing the risk of phenotype compensation and off-target effects. Trim-Away introduces exogenous TRIM21 (an E3 (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Immunotherapy: Vaccine patch to treat melanoma
Nature Reviews Drug Discovery 17, 18 (2018). doi:10.1038/nrd.2017.259 Author: Sarah Crunkhorn The use of whole tumour cell preparations in cancer immunotherapy, to simultaneously target multiple tumour antigens to activate the immune response, is a promising therapeutic approach. Ye et al. have developed a transdermal microneedle vaccine patch that directly targets antigen-presenting cells via delivery of (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer: Targeting telomeres
Nature Reviews Drug Discovery 17, 18 (2018). doi:10.1038/nrd.2017.258 Author: Sarah Crunkhorn Telomere maintenance enables the indefinite proliferation potential of cancer cells and is among the most frequent alterations in human glioblastoma (GBM). Here, Bejarano et al. report that expression of the telomere binding protein TRF1 — essential for telomere capping and protection — is upregulated (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer immunotherapy: Microbes matter
Nature Reviews Drug Discovery 17, 16 (2018). doi:10.1038/nrd.2017.265 Author: Anna Dart Preclinical mouse models have shown that the gut microbiome can modulate therapeutic responses to cancer therapies. Yet, this has not been extensively characterized in humans. Two studies now propose that the gut microbiome is an important host factor that determines the response and primary resistance (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Anna Dart Tags: Research Highlight Source Type: research

Sean Harper
Nature Reviews Drug Discovery 17, 10 (2018). doi:10.1038/nrd.2017.262 Amgen bought deCODE genetics for US$415 million in December 2012, with a plan to ramp up their use of human genetic data in drug discovery and development. This deal has since transformed Amgen's pipeline, says Amgen Chief Scientific Officer Sean Harper. A treasure trove of genetic data from more than 160,000 Icelanders now informs everything from target selection to clinical trial design. Genetic insights, sequencing capabilities and analytical expertise have helped the company to avoid costly failures, prosecute programmes more effectively and dis...
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Sage gets an antidepressant lift
Nature Reviews Drug Discovery 17, 7 (2018). doi:10.1038/nrd.2017.270 Author: Asher Mullard Sage Therapeutics' lead antidepressant brexanolone generated positive results in two phase III trials for postpartum depression, and a next-generation candidate with similar properties passed a smaller phase II trial for major depressive disorder.Brexanolone is an intravenous formulation of the steroid allopregnanolone, which is thought (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Boehringer Ingelheim experiments with open-access chemical probes
Nature Reviews Drug Discovery 17, 7 (2018). doi:10.1038/nrd.2017.269 Author: Asher Mullard Boehringer Ingelheim launched a platform to share well-characterized preclinical compounds with the biomedical community. These can be used as probes to explore mechanistic and phenotypic biology.The company is currently offering nearly 20 molecular probes through its opnME portal for free, without intellectual property (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

First in vivo gene-editing drugs enter the clinic
Nature Reviews Drug Discovery 17, 7 (2018). doi:10.1038/nrd.2017.268 Author: Asher Mullard Sangamo Therapeutics has started dosing patients with gene-editing drugs that are administered directly into the blood.Sangamo's zinc finger nucleases (ZFNs) are enzymes that selectively bind, cleave and enable the directed repair of DNA to knock genes both in and out of patient genomes. In (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

A dynamic map for learning, communicating, navigating and improving therapeutic development
Nature Reviews Drug Discovery 17, 150 (2018). doi:10.1038/nrd.2017.217 Authors: John Wagner, Andrew M. Dahlem, Lynn D. Hudson, Sharon F. Terry, Russ B. Altman, C. Taylor Gilliland, Christopher DeFeo & Christopher P. Austin Drug discovery and development is a highly challenging process (Nat. Rev. Drug Discov.9, 203–214; 2010). Its common characterization as a 'pipeline' connotes consistent unidirectional flow of a candidate therapeutic in unchanged form from basic research discovery to (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 22, 2017 Category: Drugs & Pharmacology Authors: John Wagner Andrew M. Dahlem Lynn D. Hudson Sharon F. Terry Russ B. Altman C. Taylor Gilliland Christopher DeFeo Christopher P. Austin Tags: Correspondence Source Type: research

Regulatory policy for the development of targeted therapies for low-frequency molecular subtypes of disease
Nature Reviews Drug Discovery 17, 79 (2018). doi:10.1038/nrd.2017.231 Authors: Robert N. Schuck, Michael Pacanowski, Janet Woodcock & Issam Zineh Numerous challenges arise when developing targeted therapies for diseases comprising low-frequency molecular subtypes. In this article, we describe a pragmatic, science-based regulatory policy for the development and approval of targeted therapies in such cases. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 22, 2017 Category: Drugs & Pharmacology Authors: Robert N. Schuck Michael Pacanowski Janet Woodcock Issam Zineh Tags: Comment Source Type: research

Automating drug discovery
Nature Reviews Drug Discovery 17, 97 (2018). doi:10.1038/nrd.2017.232 Author: Gisbert Schneider Small-molecule drug discovery can be viewed as a challenging multidimensional problem in which various characteristics of compounds — including efficacy, pharmacokinetics and safety — need to be optimized in parallel to provide drug candidates. Recent advances in areas such as microfluidics-assisted chemical synthesis and biological (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: Gisbert Schneider Tags: Perspectives Source Type: research

Mechanistic enzymology in drug discovery: a fresh perspective
Nature Reviews Drug Discovery 17, 78 (2018). doi:10.1038/nrd.2017.257 Author: Geoffrey A. Holdgate, Thomas D. Meek & Rachel L. Grimley Nature Reviews Drug Discovery, 10.1038/nrd.2017.219 (2017)In the affiliations of this article, the address provided for Discovery Sciences, IMED Biotech Unit, AstraZeneca was incorrect and should be Building 310, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.The article has (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: Geoffrey A. Holdgate Thomas D. Meek Rachel L. Grimley Tags: Erratum Source Type: research

Drug discovery effectiveness from the standpoint of therapeutic mechanisms and indications
Nature Reviews Drug Discovery 17, 78 (2018). doi:10.1038/nrd.2017.255 Author: Hsin-Pei Shih, Xiaodan Zhang & Alex M. Aronov Nature Reviews Drug Dicovery, 10.1038/nrd.2017.194 (2017)In Figure 3c of this article, the labels for the mechanisms were misplaced. The article has been corrected in the print and online version. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: Hsin-Pei Shih Xiaodan Zhang Alex M. Aronov Tags: Corrigendum Source Type: research

Cancer Immunotherapy: The right shape
Nature Reviews Drug Discovery 17, 18 (2018). doi:10.1038/nrd.2017.256 Author: M. Teresa Villanueva Targeting antigens expressed specifically on the cell surface of cancer cells with monoclonal antibodies (mAbs) or chimeric antigen receptor (CAR)–expressing T cells has become a successful approach in cancer therapy. Most of the cancer-specific antigens shared by multiple tumours are likely to have already been (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Infectious disease: Blocking malaria parasite invasion and egress
Nature Reviews Drug Discovery 17, 17 (2018). doi:10.1038/nrd.2017.253 Author: Sarah Crunkhorn Growing resistance of the malaria-transmitting parasite, Plasmodium falciparum, to existing therapies has increased the need for new therapeutic approaches. Two new papers in Science now report vital roles for plasmepsins IX and X (PMIX and PMX) in P. falciparum invasion and egress (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer: Strategies for mature T cell cancers
Nature Reviews Drug Discovery 17, 15 (2018). doi:10.1038/nrd.2017.254 Author: Megan Cully Cancers of mature T cells, such as T cell non-Hodgkin lymphoma (NHL), are aggressive and resistant to treatment. Two new papers provide insight into the future treatment of mature T cell cancers. Wartewig and colleagues demonstrate that PDCD1, which encodes programmed cell death protein (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 15, 2017 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research

Mechanistic enzymology in drug discovery: a fresh perspective
Nature Reviews Drug Discovery 17, 115 (2018). doi:10.1038/nrd.2017.219 Authors: Geoffrey A. Holdgate, Thomas D. Meek & Rachel L. Grimley Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 1, 2017 Category: Drugs & Pharmacology Authors: Geoffrey A. Holdgate Thomas D. Meek Rachel L. Grimley Tags: Review Source Type: research

Deal watch: Roche taps potential antibiotics mine with Warp Drive Bio
Nature Reviews Drug Discovery 17, 8 (2018). doi:10.1038/nrd.2017.247 Author: Megan Cully Roche has entered into a strategic collaboration with Warp Drive Bio to mine bacterial genomes for novel antibiotics. The terms of the agreement, worth up to US$387 million, include an option for Roche to have a worldwide license to develop certain classes of antibiotics that (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 1, 2017 Category: Drugs & Pharmacology Authors: Megan Cully Tags: News and Analysis Source Type: research

Cancer immunotherapy: Rewiring cancer cells
Nature Reviews Drug Discovery 16, 828 (2017). doi:10.1038/nrd.2017.242 Author: Anna Dart A number of factors ranging from the scarcity of tumour-specific neoantigens, tumour immunosuppression and toxicity caused by systemic delivery of immunomodulators restrict the efficiency of cancer immunotherapies. To overcome these obstacles, Nissim, Wu et al. have engineered a synthetic gene circuit enabling the production (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Anna Dart Tags: Research Highlight Source Type: research

GPCRs: Crystal structure of D4 dopamine receptor
Nature Reviews Drug Discovery 16, 828 (2017). doi:10.1038/nrd.2017.236 Author: Sarah Crunkhorn Numerous compounds are reported to interact with dopamine receptors, but the molecular mechanisms mediating dopamine receptor selectivity and activity are poorly understood. Here, Wang et al. determine crystal structures of the D4 dopamine receptor (D4R) in its inactive state bound to the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Diabetes: Selective FOXO1 modulation
Nature Reviews Drug Discovery 16, 828 (2017). doi:10.1038/nrd.2017.235 Author: Sarah Crunkhorn Inhibition of the FOXO1 transcription factor has beneficial effects on diabetic hyperglycaemia through the suppression of glucose-6-phosphatase (G6PC) activation, but it also suppresses glucokinase (GCK) inhibition, which promotes lipogenesis. Here, Langlet et al. identify SIN3A as the corepressor required for FOXO1-mediated inhibition of GCK. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Infectious disease: Fighting influenza B
Nature Reviews Drug Discovery 16, 828 (2017). doi:10.1038/nrd.2017.234 Author: Sarah Crunkhorn The use of broadly neutralizing antibodies against the influenza viral surface glycoprotein haemagglutinin (HA) represents a promising therapeutic approach. In mice, Shen et al. implemented several immunization regimens to induce cross-reactive antibodies against highly conserved epitopes in the HA protein of influenza B. A (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Polypharmacology: Repurposing ceritinib
Nature Reviews Drug Discovery 16, 828 (2017). doi:10.1038/nrd.2017.233 Author: Sarah Crunkhorn Network-based targeting strategies represent a promising therapeutic approach for the treatment of diseases that lack strong and actionable drivers. Using an integrated phenotypic screening and phosphoproteomics strategy, Kuenzi et al. report that the FDA-approved ALK inhibitor ceritinib exhibits activity in several ALK-negative non-small-cell lung (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Obesity: GDF15 tells the brain to lose weight
Nature Reviews Drug Discovery 16, 827 (2017). doi:10.1038/nrd.2017.241 Author: M. Teresa Villanueva Obesity treatments that do not involve invasive surgery are greatly needed. Now, a team of scientists from Amgen provide evidence that harnessing the activity of growth differentiation factor 15 (GDF15; also known as MIC1) can lower the body weight of obese mice and monkeys through (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

BTK inhibitors get a boost
Nature Reviews Drug Discovery 16, 818 (2017). doi:10.1038/nrd.2017.250 Author: Asher Mullard The FDA granted accelerated approval to AstraZeneca and Acerta Pharma's acalabrutinib for mantle cell lymphoma, a second approval for the BTK inhibitor class. The agency approved AbbVie and Janssen's first-in-class BTK inhibitor, ibrutinib, in 2013 for the same indication. Ibrutinib has since picked up (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Second anticancer CAR T therapy receives FDA approval
Nature Reviews Drug Discovery 16, 818 (2017). doi:10.1038/nrd.2017.249 Author: Asher Mullard The FDA's approval of Gilead Sciences and Kite Pharmaceutical's axicabtagene ciloleucel for relapsed or refractory large B cell lymphoma in October marked the second green light for the emerging chimeric antigen receptor (CAR) T cell modality. In August, the agency approved Novartis's tisagenlecleucel (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

FDA approves first digital pill
Nature Reviews Drug Discovery 16, 818 (2017). doi:10.1038/nrd.2017.248 Author: Asher Mullard The FDA approved a first drug–device product that uses a digital chip to monitor ingestion. This tracking technology could help address the costly problem of poor drug adherence in both medical practice and clinical trials, if it lives up to its promise (Nat. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Cryo-electron microscopy makes waves in pharma labs
Nature Reviews Drug Discovery 16, 815 (2017). doi:10.1038/nrd.2017.240 Author: Mark Peplow Companies hope the Nobel Prize-winning imaging methodology will reveal biomolecule characteristics that can guide drug discovery projects. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Mark Peplow Tags: News and Analysis Source Type: research

Small molecules against RNA targets attract big backers
Nature Reviews Drug Discovery 16, 813 (2017). doi:10.1038/nrd.2017.239 Author: Asher Mullard Novartis, Merck, Pfizer and biotech entrepreneurs have started working on small-molecule drugs that act on an assortment of RNA targets, hoping to unlock once undruggable targets and new biology. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Steps forward for cancer precision medicine
Nature Reviews Drug Discovery 17, 1 (2018). doi:10.1038/nrd.2017.218 Authors: Roberto Salgado, Helen Moore, John W. M. Martens, Tracy Lively, Shakun Malik, Ultan McDermott, Stefan Michiels, Jeffrey A. Moscow, Sabine Tejpar, Tawnya McKee & Denis Lacombe The availability of targeted anticancer drugs and the relative affordability of genomic analyses has led to a growing expectation among patients with cancer that they can receive personalized treatment based on the genomic signature of their tumour. Here, we discuss some of the challenges and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 24, 2017 Category: Drugs & Pharmacology Authors: Roberto Salgado Helen Moore John W. M. Martens Tracy Lively Shakun Malik Ultan McDermott Stefan Michiels Jeffrey A. Moscow Sabine Tejpar Tawnya McKee Denis Lacombe Tags: Comment Source Type: research