Malaria: Clues to vaccine design
Nature Reviews Drug Discovery 17, 316 (2018). doi:10.1038/nrd.2018.57 Author: Sarah Crunkhorn Vaccination with attenuated Plasmodium falciparum sporozoites (PfSPZs) can induce robust immune responses. However, the specific mediators of this protective immune response remain undefined. To investigate this, Seder and colleagues first isolated monoclonal antibodies directed against the Pf circumsporozoite protein (PfCSP) — which covers the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Type 2 diabetes: Targeting glutamine metabolism
Nature Reviews Drug Discovery 17, 316 (2018). doi:10.1038/nrd.2018.56 Author: Sarah Crunkhorn Reducing elevated glucagon signalling in diabetic patients is an attractive strategy for the treatment of hyperglycaemia. Using mouse primary hepatocytes, Miller and colleagues demonstrate a key contribution of glutamine to newly synthesized glucose in response to glucagon stimulation. Short hairpin RNA-mediated knockdown of hepatic glutaminase (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Neurodegeneration: New strategy for SBMA therapy
Nature Reviews Drug Discovery 17, 316 (2018). doi:10.1038/nrd.2018.55 Author: Sarah Crunkhorn Spinal bulbar muscular atrophy (SBMA) results from a polyglutamine expansion in the androgen receptor (AR). Recently, co-regulator binding through the activation function 2 (AF2) domain of the AR has been indicated as essential for pathogenesis. Here, Badders and colleagues screened a panel of small molecules (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Anticancer drugs: Flipping the switch for selective GSK3 inhibition
Nature Reviews Drug Discovery 17, 314 (2018). doi:10.1038/nrd.2018.63 Author: Katie Kingwell Glycogen synthase kinase 3 (GSK3) is a potential therapeutic target in many diseases, including cancer and neurological disorders. But clinical trials of dual GSK3α/β inhibitors have not proved successful, and there is concern about on-target liabilities related to β-catenin signalling. Now, Wagner, Stegmaier and colleagues (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Katie Kingwell Tags: Research Highlight Source Type: research

Anja K ö nig
Nature Reviews Drug Discovery 17, 310 (2018). doi:10.1038/nrd.2018.60 When Anja König started her PhD in mathematical physics at Cornell University, she hoped that a pencil and a brain was all she'd need to tackle hard science questions. Over two decades on, she has now swapped the pencil for a chequebook and moved into the much more empirical world of life sciences. As Global Head of the Novartis Venture Fund (NVF), she oversees one of the most deep-pocketed and active corporate venture capital (CVC) funds in biopharma. NVF — a financially rather than strategically driven CVC group — has around US$80...
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Regulatory watch: FDA new drug approvals in Q1 2018
Nature Reviews Drug Discovery 17, 309 (2018). doi:10.1038/nrd.2018.61 Author: Lisa Urquhart The first quarter of the year saw two notable FDA approvals for HIV therapies. In early February, Gilead Sciences gained approval for its triple combination product Biktarvy, which brings together the novel HIV-1 integrase inhibitor bictegravir with the established dual nucleoside reverse transcriptase inhibitor (NRTI) (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Lisa Urquhart Tags: News and Analysis Source Type: research

Cashing in with off-the-shelf CAR Ts
Nature Reviews Drug Discovery 17, 307 (2018). doi:10.1038/nrd.2018.69 Author: Asher Mullard Allogene Therapeutics is taking over rights to Pfizer's off-the-shelf chimeric antigen receptor (CAR) T cell pipeline, backed by US$300 million from one of the largest series A funding rounds in the history of biotech.Last year the FDA approved the first ever CAR Ts, (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Novartis grows its gene therapy ambitions
Nature Reviews Drug Discovery 17, 307 (2018). doi:10.1038/nrd.2018.68 Author: Asher Mullard Novartis is buying gene therapy company AveXis for US$8.7 billion, expanding its gene therapy capabilities.AveXis's lead candidate is AVXS-101, a recombinant AAV9-based gene therapy for the treatment of spinal muscular atrophy (SMA). SMA is a neuromuscular disease that is caused by genetic defects in (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

IDO takes a blow
Nature Reviews Drug Discovery 17, 307 (2018). doi:10.1038/nrd.2018.67 Author: Asher Mullard Incyte's epacadostat and Merck & Co's pembrolizumab failed in a phase III combination study in unresectable and metastatic melanoma, the companies reported in April, dealing a major blow to hopes for the would-be first-in-class IDO inhibitor.Whereas most of the immuno-oncology research to date (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Industry embraces virtual trial platforms
Nature Reviews Drug Discovery 17, 305 (2018). doi:10.1038/nrd.2018.66 Author: Elie Dolgin Site-less trials promise to speed up drug development — but obstacles to in-home data collection abound. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Elie Dolgin Tags: News and Analysis Source Type: research

Microglia-targeted candidates push the Alzheimer drug envelope
Nature Reviews Drug Discovery 17, 303 (2018). doi:10.1038/nrd.2018.65 Author: Asher Mullard Denali Therapeutics is taking a swing at neuroinflammation with a first-in-man trial of a RIPK1 inhibitor, while the company and others search for ways to target microglial biology more precisely. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 27, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

Accelerating the development of therapeutic strategies for drug-resistant tuberculosis
Nature Reviews Drug Discovery 17, 377 (2018). doi:10.1038/nrd.2018.64 Author: Michael J. Vjecha, Simon Tiberi & Alimuddin Zumla Nature Reviews Drug Discovery (2018); doi:10.1038/nrd.2018.28The affiliations for Michael J. Vjecha have been modified. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 20, 2018 Category: Drugs & Pharmacology Authors: Michael J. Vjecha Simon Tiberi Alimuddin Zumla Tags: Corrigendum Source Type: research

Cancer: Mopping up a molecule for breast cancer survival
Nature Reviews Drug Discovery 17, 316 (2018). doi:10.1038/nrd.2018.58 Author: Megan Cully Many cancers suppress immune surveillance to avoid an antitumour response. However, scientists have reported in Nature Immunology that breast cancer cells promote immune cell infiltration, and that infiltrating myeloid cells can be usurped to promote breast cancer cell survival. Thymic stromal lymphopoietin (TSLP) produced (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 20, 2018 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research

Metabolic disease: Liver enzyme inflames fat
Nature Reviews Drug Discovery 17, 315 (2018). doi:10.1038/nrd.2018.59 Author: Sarah Crunkhorn Obesity-induced activation of adipose tissue inflammation is closely correlated with insulin resistance, but the mechanisms mediating such pathological inflammation are poorly understood. Writing in Nature, Tabas, Ozcan and colleagues report that in mice, obesity stimulates hepatocytes to secrete the enzyme dipeptidyl peptidase 4 (DPP4), (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 20, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer immunotherapy: The perfect match
Nature Reviews Drug Discovery 17, 313 (2018). doi:10.1038/nrd.2018.62 Author: M. Teresa Villanueva Interleukin-2 (IL-2) is a cytokine required in both mounting and dampening immune responses. IL-2 is involved in the expansion, survival and activation of effector T cells and has been used in combination with adoptive transfer of T cells in cancer to overcome some of the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 20, 2018 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Senotherapeutics for healthy ageing
Nature Reviews Drug Discovery 17, 377 (2018). doi:10.1038/nrd.2018.44 Authors: Laura J. Niedernhofer & Paul D. Robbins The recent manuscript by Childs et al. in Nature Reviews Drug Discovery thoroughly reviewed the important role senescent cells play in driving ageing and age-related diseases. The review also highlighted the clinical importance of developing senotherapeutic approaches to selectively kill senescent cells (senolytics) (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 13, 2018 Category: Drugs & Pharmacology Authors: Laura J. Niedernhofer Paul D. Robbins Tags: Correspondence Source Type: research

Chemical probes and drug leads from advances in synthetic planning and methodology
Nature Reviews Drug Discovery 17, 333 (2018). doi:10.1038/nrd.2018.53 Authors: Christopher J. Gerry & Stuart L. Schreiber Screening of small-molecule libraries is a productive method for identifying both chemical probes of disease-related targets and potential starting points for drug discovery. In this article, we focus on strategies such as diversity-oriented synthesis that aim to explore novel areas of chemical space efficiently by (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 13, 2018 Category: Drugs & Pharmacology Authors: Christopher J. Gerry Stuart L. Schreiber Tags: Review Source Type: research

The gastroesophageal cancer drug market
Nature Reviews Drug Discovery 17, 311 (2018). doi:10.1038/nrd.2018.35 Authors: Paul Wilcock & Rachel M. Webster Immune checkpoint inhibitors are forecast to expand the market for gastroesophageal cancer drugs, which is particularly large in Asia. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - April 3, 2018 Category: Drugs & Pharmacology Authors: Paul Wilcock Rachel M. Webster Tags: News and Analysis Source Type: research

Infectious disease: Virus-based tuberculosis vaccine
Nature Reviews Drug Discovery 17, 242 (2018). doi:10.1038/nrd.2018.50 Author: Sarah Crunkhorn The bacille Calmette–Guérin vaccine can protect children from tuberculosis (TB), but is not effective in adults, probably owing to Mycobacterium tuberculosis (Mtb) manipulating human innate immune responses to enable persistent infection. A recent study reports a promising alternative vaccine approach — the use of (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Sepsis: Gut bacteria induce protective IgA
Nature Reviews Drug Discovery 17, 242 (2018). doi:10.1038/nrd.2018.49 Author: Sarah Crunkhorn The mechanisms mediating serum immunoglobulin A (IgA) responses and their potential role in protective immunity remain unknown. Wilmore and colleagues show that members of the Proteobacteria phylum in the gut of mice promote a T cell-dependent increase in serum IgA and IgA-secreting bone marrow plasma (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Immunotherapy: iPSC-based cancer vaccine
Nature Reviews Drug Discovery 17, 242 (2018). doi:10.1038/nrd.2018.48 Author: Sarah Crunkhorn Pluripotent cells share antigens with cancer cells, suggesting that they could be used to prime the immune system to target cancer. Here, Kooreman and colleagues report the development of a vaccine based on irradiated mouse induced pluripotent stem cells. Prophylactically, the vaccine inhibited tumour growth (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Antivirals: Topical therapy for ocular herpes
Nature Reviews Drug Discovery 17, 242 (2018). doi:10.1038/nrd.2018.47 Author: Sarah Crunkhorn Nucleoside analogue-based drugs control herpes simplex virus type 1 (HSV-1) infection of the eye, but are limited by potential drug resistance and adverse effects. Jaishankar and colleagues report that the small-molecule TANK-binding kinase 1 (TBK1) inhibitor, BX795, suppresses HSV-1 infection in transformed and primary human (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Drug delivery: DNA nanorobots — seek and destroy
Nature Reviews Drug Discovery 17, 242 (2018). doi:10.1038/nrd.2018.40 Author: Conor A. Bradley Due to the potential of DNA molecules as substrates for the production of molecular machines with biological functionality, there is much interest in using DNA-based nanorobotic systems for the targeted delivery of therapeutic payloads to tumours. A new study reports the development of autonomous 'DNA (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Conor A. Bradley Tags: Research Highlight Source Type: research

Neurodevelopmental disorders: CRISPR to the rescue
Nature Reviews Drug Discovery 17, 240 (2018). doi:10.1038/nrd.2018.39 Author: M. Teresa Villanueva Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a CGG repeat expansion in the promoter region of FMR1. This mutation results in hypermethylation and silencing of FMR1 and absence, or reduction, of its gene product, fragile X mental retardation protein 1 (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

George Yancopoulos
Nature Reviews Drug Discovery 17, 234 (2018). doi:10.1038/nrd.2018.41 When Leonard Schleifer recruited George Yancopoulos as CSO of Regeneron in 1988, Schleifer was running the company out of a one-bedroom apartment in New York City. Thirty years on, the company has brought six drugs to the US market, and has a pipeline of more than fifteen antibody therapies in development across cardiovascular disease, infectious disease, inflammation, immunology, oncology and more. Yancopoulos credits this success to stable management, a commitment to in-house science, end-to-end drug discovery and development capabilities, and gen...
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Market watch: Upcoming market catalysts in Q2 2018
Nature Reviews Drug Discovery 17, 233 (2018). doi:10.1038/nrd.2018.43 Author: Alexandra Heller Potential market catalysts in the second quarter of 2018 include top-line clinical trial results for NEOD001 (developed by Prothena) for light-chain (AL) amyloidosis and ALXN1210 (developed by Alexion) for paroxysmal nocturnal haemoglobinuria (PNH), as well as an FDA advisory committee meeting on volanesorsen (developed by (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Alexandra Heller Tags: News and Analysis Source Type: research

Market watch: Top drugs and companies by sales in 2017
Nature Reviews Drug Discovery 17, 232 (2018). doi:10.1038/nrd.2018.42 Author: Lisa Urquhart A look at the best-selling drugs in 2017 shows the top spots dominated by monoclonal antibodies which, despite their age and looming competition, are still pulling in billions of dollars (Fig. 1a). The success of these huge franchises is partly down to the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 28, 2018 Category: Drugs & Pharmacology Authors: Lisa Urquhart Tags: News and Analysis Source Type: research

Unexplored therapeutic opportunities in the human genome
Nature Reviews Drug Discovery 17, 377 (2018). doi:10.1038/nrd.2018.52 Author: Tudor I. Oprea, Cristian G. Bologa, Søren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Steven L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schürer, Anton Simeonov, Larry A. Sklar, Noel Sou...
Source: Nature Reviews Drug Discovery - March 23, 2018 Category: Drugs & Pharmacology Authors: Tudor I. Oprea Cristian G. Bologa S ø ren Brunak Allen Campbell Gregory N. Gan Anna Gaulton Shawn M. Gomez Rajarshi Guha Anne Hersey Jayme Holmes Ajit Jadhav Lars Juhl Jensen Gary L. Johnson Anneli Karlson Andrew R. Leach Avi Ma'ayan Anna Malovannaya Sub Tags: Corrigendum Source Type: research

Unexplored therapeutic opportunities in the human genome
Nature Reviews Drug Discovery 17, 317 (2018). doi:10.1038/nrd.2018.14 Authors: Tudor I. Oprea, Cristian G. Bologa, Søren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schürer, Anton Simeonov, Larry A. Sklar, Noel S...
Source: Nature Reviews Drug Discovery - March 23, 2018 Category: Drugs & Pharmacology Authors: Tudor I. Oprea Cristian G. Bologa S ø ren Brunak Allen Campbell Gregory N. Gan Anna Gaulton Shawn M. Gomez Rajarshi Guha Anne Hersey Jayme Holmes Ajit Jadhav Lars Juhl Jensen Gary L. Johnson Anneli Karlson Andrew R. Leach Avi Ma'ayan Anna Malovannaya Sub Tags: Analysis Source Type: research

Kinase inhibitors: the road ahead
Nature Reviews Drug Discovery 17, 353 (2018). doi:10.1038/nrd.2018.21 Authors: Fleur M. Ferguson & Nathanael S. Gray Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been firmly demonstrated to play an essential role in virtually all major disease areas. Kinase inhibitor drug discovery programmes have recently broadened their focus (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 16, 2018 Category: Drugs & Pharmacology Authors: Fleur M. Ferguson Nathanael S. Gray Tags: Review Source Type: research

Asthma: Alternative route to airway relaxation
Nature Reviews Drug Discovery 17, 241 (2018). doi:10.1038/nrd.2018.37 Author: Sarah Crunkhorn Promoting airway smooth muscle cell (ASMC) relaxation is an established therapeutic strategy for alleviating pulmonary resistance in asthma. However, current approaches, which involve the inhalation of β2-adrenoceptor agonists, do not adequately control symptoms in all patients and are associated with side effects. Writing (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 16, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Antibacterial drugs: Discovering antibiotics through soil metagenomics
Nature Reviews Drug Discovery 17, 240 (2018). doi:10.1038/nrd.2018.36 Author: Katharine H. Wrighton The identification of bacterial natural products with antimicrobial properties has been hampered by the fact that many bacteria cannot be cultured in the laboratory, and those that can do not produce all of their natural products in this setting. Hover et al. have devised a (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 16, 2018 Category: Drugs & Pharmacology Authors: Katharine H. Wrighton Tags: Research Highlight Source Type: research

Cancer: Tipping the splicing balance to kill cancer cells
Nature Reviews Drug Discovery 17, 239 (2018). doi:10.1038/nrd.2018.38 Author: Megan Cully Mutations in genes encoding splicing factors are commonly found in samples from patients with several haematological cancers, as well as some solid tumours. A new paper in Nature Medicine describes a novel, orally available splicing modulator that preferentially kills cancer cells with mutations in (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 16, 2018 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research

Vaccines take a shot at antimicrobial resistance
Nature Reviews Drug Discovery 17, 229 (2018). doi:10.1038/nrd.2018.8 Author: Katie Kingwell Economic and policy issues rein in industry enthusiasm for vaccines as an answer to drug-resistant bugs. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 9, 2018 Category: Drugs & Pharmacology Authors: Katie Kingwell Tags: News and Analysis Source Type: research

Tissue-agnostic cancer drug pipeline grows, despite doubts
Nature Reviews Drug Discovery 17, 227 (2018). doi:10.1038/nrd.2018.6 Author: Ken Garber The FDA could soon approve the first drug developed explicitly for a tissue-agnostic cancer indication, but biological complexity may limit this approach. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - March 9, 2018 Category: Drugs & Pharmacology Authors: Ken Garber Tags: News and Analysis Source Type: research

Cancer: Targeting the ubiquitin pathway
Nature Reviews Drug Discovery 17, 166 (2018). doi:10.1038/nrd.2018.33 Author: Sarah Crunkhorn Aberrations in the ubiquitin–proteasome system — which maintains cellular protein homeostasis — are implicated in tumour development and progression. Here, Hyer et al. report the identification of TAK-243, a first-in-class inhibitor of the ubiquitin-activating enzyme. In vitro, TAK-243 induced defective protein turnover and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Alzheimer disease: Identification of blood-based biomarkers
Nature Reviews Drug Discovery 17, 166 (2018). doi:10.1038/nrd.2018.32 Author: Sarah Crunkhorn There is a significant need for a minimally invasive, cost-effective and reliable method to diagnose early-stage Alzheimer disease. Building on previous work, Nakamura et al. demonstrate the use of immunoprecipitation coupled with mass spectrometry to measure plasma amyloid-β (Aβ) biomarkers. Using two independent data (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Antibacterials: Synthetic peptides eradicate resistant infections
Nature Reviews Drug Discovery 17, 166 (2018). doi:10.1038/nrd.2018.31 Author: Sarah Crunkhorn Synthetic peptides based on naturally occurring antimicrobial peptides (AMPs) represent promising antibacterial agents. Now, de Breij and colleagues have synthesized novel peptides with improved antimicrobial and antibiofilm activities (SAAPs), based on a principle human AMP, LL-37. The most potent of these, SAAP-148, was effective against (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cardiovascular disease: Inhalation therapy for heart failure
Nature Reviews Drug Discovery 17, 166 (2018). doi:10.1038/nrd.2018.30 Author: Sarah Crunkhorn Drug delivery via inhalation is commonly used for respiratory disorders, but its potential for therapeutically targeting the heart has not been explored. Here, Miragoli et al. demonstrate in mice that following inhalation, their previously reported small, biocompatible and biodegradable negatively charged calcium phosphate nanoparticles (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Immunotherapy: Direct shot
Nature Reviews Drug Discovery 17, 165 (2018). doi:10.1038/nrd.2018.29 Author: Lucy Bird Harnessing the immune system to fight tumours is providing real hope in treating patients with cancer. Yet several immunotherapy approaches are limited by the need for prior knowledge of tumour antigens or large doses of expensive antibodies. In a recent study published in Science Translational (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Lucy Bird Tags: Research Highlight Source Type: research

Fiona Marshall
Nature Reviews Drug Discovery 17, 158 (2018). doi:10.1038/nrd.2018.25 Fiona Marshall co-founded Heptares in 2007 to apply structure-based drug design to G protein-coupled receptor (GPCR) targets, a large class of membrane-bound signalling receptors with diverse and critical roles across disease areas. Although around 35% of approved drugs act on GPCR targets, the research community had only solved the structure of a single GPCR at the time the company launched. Heptares has since determined more than 200 GPCR–ligand structures for 20 different GPCRs, advanced 4 drug candidates into the clinic, and partnered with...
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Alnylam prepares to land first RNAi drug approval
Nature Reviews Drug Discovery 17, 156 (2018). doi:10.1038/nrd.2018.20 Author: Chris Morrison With Alnylam's rare disease drug candidate patisiran nearing the regulatory finish line, the RNA interference community is now turning its attention to next-generation delivery technology to solidify the future of the emerging modality. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 28, 2018 Category: Drugs & Pharmacology Authors: Chris Morrison Tags: News and Analysis Source Type: research

Impact of target interactions on small-molecule drug disposition: an overlooked area
Nature Reviews Drug Discovery 17, 299 (2018). doi:10.1038/nrd.2018.26 Authors: Robert A. B. van Waterschoot, Neil J. Parrott, Andrés Olivares-Morales, Thierry Lavé, Malcolm Rowland & Dennis A. Smith The selection of an appropriate drug target, as well as a solid understanding of drug pharmacokinetics and pharmacodynamics, are crucial for successful drug discovery. Although it is generally accepted that the free (unbound) concentration of a drug is the driving force for its pharmacological (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 23, 2018 Category: Drugs & Pharmacology Authors: Robert A. B. van Waterschoot Neil J. Parrott Andr é s Olivares-Morales Thierry Lav é Malcolm Rowland Dennis A. Smith Tags: Correspondence Source Type: research

Cancer: Reset your circadian clock
Nature Reviews Drug Discovery 17, 166 (2018). doi:10.1038/nrd.2018.24 Author: M. Teresa Villanueva The circadian clock controls several physiological functions, such as metabolism, cell proliferation and inflammation. Now, writing in Nature, Sulli et al. report that pharmacological targeting of the circadian clock components REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), which are (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 16, 2018 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research

Cancer: New path to improving immunotherapy
Nature Reviews Drug Discovery 17, 164 (2018). doi:10.1038/nrd.2018.22 Author: Sarah Crunkhorn Cancer patients with high levels of circulating myeloid-derived suppressor cells (MDSCs) have been found to respond poorly to checkpoint blockade. Accordingly, there is significant interest in therapeutically targeting these immunosuppressive innate immune cells. Writing in Cell, lead author Masoud Tavazoie and colleagues now report (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 16, 2018 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Cancer: Fibroblast subtype provides niche for cancer stem cells
Nature Reviews Drug Discovery 17, 163 (2018). doi:10.1038/nrd.2018.23 Author: Megan Cully The role of cancer-associated fibroblasts (CAFs) in tumour formation has been controversial. A new paper in Cell demonstrates that a subset of CAFs, defined by the presence of the cell surface markers CD10 and GPR77, promotes tumour formation and chemoresistance by providing a niche (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 16, 2018 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research

Oncologists tap the microbiome in bid to improve immunotherapy outcomes
Nature Reviews Drug Discovery 17, 153 (2018). doi:10.1038/nrd.2018.19 Author: Asher Mullard A pioneering Merck & Co.-funded study is set to explore the ability of the microbiome to boost immuno-oncology therapy outcomes, and other companies are quickly gearing up to enter this clinical space. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - February 16, 2018 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research

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