Applications of chemogenomic library screening in drug discoveryNat. Rev. Drug. Disc ( IF 47.120 ) 2017-01-20
Lyn H. Jones, Mark E. Bunnage
Chemogenomic screening is increasingly being applied to expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Here, Jones and Bunnage discuss the principles of the creation and use of chemogenomic libraries, highlighting key examples and their applications, including target identification, drug repositioning and predictive toxicology.
The SCCHN drug marketNat. Rev. Drug. Disc ( IF 47.120 ) 2017-01-13
Jennifer Bamford, Rachel M. Webster
Two PD-1 directed checkpoint inhibitors have recently been approved for squamous cell carcinoma of the head and neck (SCCHN). Further checkpoint inhibitors, as well as other molecularly targeted agents and cytokine-based immunotherapies, are currently in the late-stage pipeline and are poised to change the treatment paradigm for SCCHN.
Strategies for delivering value from digital technology transformationNat. Rev. Drug. Disc ( IF 47.120 ) 2017-01-13
Eric D. Perakslis
Many organizations are attempting to harness emerging digital technologies and the surge in the amount of health-related data to drive advances in the development and use of medicines. Focusing on just a few well-proven and readily available strategies could enable such organizations to quickly realize greater value from data and digital technologies.
Dynamic versus static biomarkers in cancer immune checkpoint blockade: unravelling complexityNat. Rev. Drug. Disc ( IF 47.120 ) 2017-01-06
W. Joost Lesterhuis, Anthony Bosco, Michael J. Millward, Michael Small, Anna K. Nowak, Richard A. Lake
Immune checkpoint blockade is a powerful anticancer approach; however, it only works for some patients. Here, Lesterhuis and colleagues argue that response to immune checkpoint blockade is a critical state transition of a complex system. They discuss recent advances in mathematics and network biology that might facilitate the identification of dynamic biomarkers, which in turn might help distinguish responders from non-responders and determine new targets for combination therapy.
Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseasesNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
John A. Hamilton, Andrew D. Cook, Paul P. Tak
Granulocyte–macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF; also known as CSF1), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) can each play a part in the host response to injury and infection, and there is burgeoning interest in targeting these CSFs in inflammatory and autoimmune
Diabetes: Turning down galectin 3 to combat insulin resistanceNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Insulin resistance is a hallmark of type 2 diabetes and is associated with inflammation of insulin target tissues such as adipose tissue, muscle and liver. A recent study by Olefsky and colleagues has shown that galectin 3 (GAL3) provides a crucial mechanistic link between inflammation
Computational chemistry: Novel virtual screening approachNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Structure-based drug discovery methods are generally based on predicting the binding affinity of a ligand to a protein. Ruiz-Carmona et al. introduce a novel computational procedure termed dynamic undocking (DUck), which evaluates the structural stability of protein–ligand complexes. DUck calculates the work needed to
Alzheimer disease: BACE1 inhibitor reduces β-amyloid production in humansNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Inhibition of aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1), required for production of β-amyloid (Aβ) peptides, is an attractive approach to lower Aβ levels in AD. Kennedy et al. present verubecestat (MK-8931), the first BACE1 inhibitor to reach phase III clinical
Antibacterials: Microcins limit intestinal infectionNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Small proteins known as microcins that are secreted from commensal intestinal bacteria exhibit antibacterial properties in vitro. Sassone-Corsi et al. now show in mouse colitis models, that inoculation with a probiotic microcin-secreting Escherichia coli strain (EcN) outcompetes and limits gut colonization with
Cardiovascular disease: Dietary supplement protects the heartNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Ageing is typically associated with cardiac hypertrophy and decline of diastolic function. Eisenberg et al. report that dietary supplementation with the natural polyamine spermidine significantly extends the median lifespan of mice. Moreover, in aged mice, spermidine reversed age-associated hypertrophy and improved cardiac diastolic function
Cancer: Microtubule-straightening compound widens the therapeutic windowNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Microtubule-targeting agents (MTAs) are standard-of care chemotherapeutics for a wide range of cancers, but their use is limited by side effects such as neuropathy. Now, reporting in Science Translational Medicine, Brouhard, Roulston and colleagues present a novel small-molecule MTA that has potent antitumour activity
Anticancer drugs: Switching off immune suppressionNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Two papers have shown in mouse tumour models that targeting PI3Kγ in myeloid cells can reduce immune suppression and increase the efficacy of immune checkpoint inhibitors.Kaneda et al. first examined data from The Cancer Genome Atlas on head and neck squamous cell carcinoma
Drug delivery: Star-shaped pill sustains drug releaseNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Long-acting sustained-release oral therapies have the potential to substantially improve patient adherence and reduce side effects. However, the development of such therapeutics is limited by a rapid gastrointestinal (GI) transit time. Now, writing in Science Translational Medicine, Traverso, Langer and colleagues report the design
Anticancer drugs: Cutting the antioxidant supply chainNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
The reducing agent glutathione is particularly important to cancer cells, as the expression of oncogenes and the high rates of metabolism in these cells result in the production of excessive quantities of reactive oxygen species (ROS). Cramer et al. now report a novel therapeutic
John LechleiterNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
John Lechleiter started working at Eli Lilly in a research laboratory, as an organic chemist, in 1979. Over the next three decades, he climbed the management ladder all the way to the top, becoming Chief Executive Officer (CEO) of the large pharmaceutical company in 2008. In December, after 37 years at Lilly, Lechleiter retired. He spoke with Asher Mullard about his career path, the prospects for chemists with their eyes on the executive suite and his high-risk, high-reward bets on Alzheimer disease drug development.
Market watch: Upcoming market catalysts in Q1 2017Nat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Potentially important market catalysts in the first quarter of 2017 include top-line phase IIb/III trial results for PRO 140 (developed by CytoDyn, Progenics Pharmaceuticals and PDL BioPharma) in highly treatment-experienced patients with HIV and top-line phase II/III trial results for CR845 (developed by Cara Therapeutics,
Cures Act shakes up the FDA and NIHNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
President Barack Obama signed the 312-page 21st Century Cures Actinto law, bringing sweeping changes to both the FDA and NIH.One of the broadest changes in the Act is that the FDA must work to incorporate real world data into its regulatory decision-making processes.
R&D returns continue to fallNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Big pharma's return on investment for R&D expenditure fell to 3.7% in 2016, shows an annual report from Deloitte (Fig. 1). This marks a low point since the consultants started tracking these data in 2010.The analysis tracks the R&D returns of
3D cell technologies head to the R&D assembly lineNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Organs-on-chips and organoids are set to start addressing key drug discovery bottlenecks.
Alzheimer amyloid hypothesis lives onNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-29
Despite the failure of Eli Lilly's anti-amyloid antibody solanezumab in its latest phase III trial for Alzheimer disease, a bulging pipeline of amyloid-modulating candidates and novel clinical trial strategies still hold promise.
Cornerstones of CRISPR–Cas in drug discovery and therapyNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-23
Christof Fellmann, Benjamin G. Gowen, Pei-Chun Lin, Jennifer A. Doudna, Jacob E. Corn
The use of CRISPR–Cas technology for gene editing has rapidly become widespread. Here, Corn and colleagues discuss the applications of this revolutionary tool in drug discovery and development, describing how it could make substantial contributions to target identification and validation, animal models and cell-based therapies.
Advances in islet encapsulation technologiesNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-23
Tejal Desai, Lonnie D. Shea
Islet transplantation can be an effective therapy for patients with type 1 diabetes, but its widespread use is limited by the need for lifelong immunosuppression. Here, Desai and Shea discuss the emerging potential of islet cell encapsulation including new strategies, assess key challenges facing the human translation of this technology and highlight encapsulation devices that have entered the clinic.
Induced pluripotent stem cell technology: a decade of progressNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-16
Yanhong Shi, Haruhisa Inoue, Joseph C. Wu, Shinya Yamanaka
Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, human iPSCs have been widely used for disease modelling, drug discovery and cell therapy development. This article discusses progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, including the powerful combination of human iPSC technology with recent developments in gene editing.
Trial watch: Opportunities and challenges of the 2016 target landscapeNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-16
Kyle Lafferty-Whyte, David Mormeneo, Montse del Fresno Marimon
Trial watch: Opportunities and challenges of the 2016 target landscape
DNA-encoded chemistry: enabling the deeper sampling of chemical spaceNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-09
Robert A. Goodnow, Christoph E. Dumelin, Anthony D. Keefe
DNA-encoded chemistry enables rapid and inexpensive syntheses and screening of vast chemical libraries, and is generating substantial interest and investment in the pharmaceutical industry. Here, Goodnow and colleagues provide an overview of the steps involved in the generation of DNA-encoded libraries, highlighting key applications and future directions for this technology.
A comprehensive map of molecular drug targetsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-02
Rita Santos, Oleg Ursu, Anna Gaulton, A. Patrícia Bento, Ramesh S. Donadi, Cristian G. Bologa, Anneli Karlsson, Bissan Al-Lazikani, Anne Hersey, Tudor I. Oprea, John P. Overington
The success of mechanism-based drug discovery depends on the definition of the drug target, but targets are often poorly defined in the literature. Here, Overington and colleagues present a comprehensive map of the molecular targets of approved drugs, and explore aspects including the footprint of target classes across disease areas, the success of privileged target families and drug target orthologues across standard model organisms.
Drug launch curves in the modern eraNat. Rev. Drug. Disc ( IF 47.120 ) 2016-12-02
Seth Robey, Frank S. David
The shape of the predicted sales launch curve can dramatically affect financial models of pre-commercial drugs. This article provides an update on a commonly used framework for modelling launch curves.
Anticancer drugs: Breaking up a pro-survival interactionNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
The pro-survival protein myeloid cell leukaemia 1 (MCL1) is overexpressed in many different types of cancer, but development of small molecule inhibitors for this protein has been challenging. Now, reporting in Nature, Olivier Geneste and colleagues describe a highly specific and potent small molecule
Anticancer drugs: Exploiting a weakness in colorectal cancersNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Over 80% of colorectal cancers (CRCs) contain mutations in adenomatous polyposis coli (APC), and more than 90% of these mutations result in the production of truncated proteins. Using a small-molecule screen, Zhang and colleagues have now identified a compound that selectively kills cells
Biologics: Engineering T cells for customized therapeutic responsesNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Chimeric antigen receptor (CAR) T cells are a promising type of cancer immunotherapy in which T cells are engineered to express receptors for tumour-specific antigens, thereby unleashing a cytotoxic immune response against cancer cells. However, the effect of such treatment is limited to the natural
Carole HoNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
More than 98% of the Alzheimer disease candidates that make it into phase III trials subsequently fail, according to a 2014 review of the field. Failure rates for Parkinson disease and amyotrophic lateral sclerosis (ALS) drug candidates are similarly dire. And yet, the 1.5-year-old biotechnology company Denali Therapeutics has already raised a massive US$349 million to tackle these and other neurodegenerative diseases. The company is about to advance its first candidate into the clinic, and Chief Medical Officer Carole Ho, former vice-president of early clinical development at Genentech, is making plans. She tells Asher Mullard that genetic insights into the biology of neurodegenerative disease could provide new therapeutics within 10 years.
Regulatory watch: Challenges in drug development for central nervous system disorders: a European Medicines Agency perspectiveNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Florence Butlen-Ducuing, Frank Pétavy, Lorenzo Guizzaro, Malgorzata Zienowicz, Manuel Haas, Enrica Alteri, Tomas Salmonson, Emmanuelle Corruble
Drug development for central nervous system (CNS) disorders is challenging, and a higher attrition rate compared with non-CNS drugs has been reported (Nat. Rev. Drug Discov.14, 815–816; 2015). With the aim of improving the understanding of these challenges, we analysed the
Access to medicines report cardsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Drug companies are getting moderately better at enabling access to drugs for people in low- and middle-income countries shows a recent report from the non-profit Access to Medicine Foundation.GlaxoSmithKline topped the biennial ranking, for the 5th consecutive time, followed by Johnson & Johnson
EMA opens its data vaultsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
European regulators have started publishing the full clinical trial reports for drugs that are approved for use in the European Union. Results can be accessed at https://clinicaldata.ema.europa.eu/web/cdp/home.As Nature Reviews Drug Discovery went to press, the agency had released data for only two
PCSK9 pipelineNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Promising phase II data from The Medicines Company's inclisiran have paved the way for phase III trials of a long-acting oligonucleotide-based PCSK9 inhibitor. Although the FDA has already approved two PCSK9 blockers — Amgen's evolocumab and Sanofi and Regeneron's alirocumab — these subcutaneously delivered lipid-lowering
FDA approves antitoxin antibodyNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
The FDA has approved Merck & Co's bezlotoxumab to reduce the recurrence of Clostridium difficile infection, marking the first approval for a new approach to the treatment of bacterial infections. Unlike antibiotics, which kill pathogenic bacteria, bezlotoxumab is an antibody that mops up toxins
Cancer immunology community seeks better end pointsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Drug developers are still hunting for surrogate end points that can better capture the benefits of checkpoint inhibitors, oncolytic viruses and modified T cell therapies.
Paring down the placebo responseNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-29
Pivotal trials of Alkermes's antidepressant ALKS 5461 show how a patented clinical trial design might be able to help control problematic placebo responses.
Genome-wide association studies of drug response and toxicity: an opportunity for genome medicineNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-25
Kathleen M. Giacomini, Sook Wah Yee, Taisei Mushiroda, Richard M. Weinshilboum, Mark J. Ratain, Michiaki Kubo
Genome-wide association studies of drug response and toxicity: an opportunity for genome medicine
Induced protein degradation: an emerging drug discovery paradigmNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-25
Ashton C. Lai, Craig M. Crews
Small-molecule drug discovery has traditionally focused on occupancy of a binding site that directly affects protein function. This article discusses emerging technologies, such as proteolysis-targeting chimaeras (PROTACs), that exploit cellular quality control machinery to selectively degrade target proteins, which could have advantages over traditional approaches, including the potential to target proteins that are not currently therapeutically tractable.
Drug design: Cannabinoid receptor structure revealedNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
Cannabinoid receptor 1 (CB1) represents a promising therapeutic target for a wide range of disorders. However, the molecular details that define the binding modes of both endogenous and pharmacological ligands have remained poorly understood. Now, Hua et al. have solved the crystal structure of
HIV: Achieving sustained remissionNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
Antiretroviral therapy (ART) effectively suppresses HIV replication; however, lifelong treatment is associated with toxicity and, once ART is withdrawn, the virus rebounds. Persistent viral reservoirs form rapidly during acute HIV infection owing to high levels of viral replication in gastrointestinal tissues (GITs) and severe depletion
Antibacterial agents: Microbiome-derived antibiotic identifiedNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
New antibiotics are urgently needed to tackle the growing problem of drug resistance. To identify potential novel antimicrobials, Chu et al. have deployed bioinformatic modelling and chemical synthesis to generate natural product structures from gene clusters that are predicted to encode non-ribosomal peptides (complex
Cancer: Blocking metastasisNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
Neutrophil extracellular traps (NETs), made of processed chromatin bound to cytotoxic enzymes, are released by neutrophils into the extracellular space to control microbial infections. However, NETs have also been implicated in cancer metastasis. Here, Park et al. observe NET formation in a mouse model
Immune disorders: Blocking the alternative complement pathwayNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
The complement system is a key component of the innate immune system, which constitutes an effective first line of defence against invading pathogens. However, inappropriate or uncontrolled complement activation can be deleterious and has been implicated in various diseases. Now, writing in Nature Chemical Biology
Metabolic disorders: Hormone conjugate combats metabolic syndromeNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
Dyslipidaemia, the elevation of plasma cholesterol and/or triglycerides, is a central risk factor for metabolic syndrome and can lead to insulin resistance, fatty liver and atherosclerosis. Although therapies exist to treat these conditions, such agents are often associated with side effects, and drug combinations are
Market watch: Antibacterial innovation in European SMEsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-18
There is a severe innovation gap in antibiotic R&D, and the field faces two daunting challenges. First, the discovery of novel antibiotics with no pre-existing cross- and co-resistance, and with a very low potential for emergence of resistance, presents considerable scientific obstacles, especially for Gram-negative
Calpain research for drug discovery: challenges and potentialNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-11
Yasuko Ono, Takaomi C. Saido, Hiroyuki Sorimachi
The calpain family of proteases are involved in numerous physiological and pathological processes. Here, Sorimachi and colleagues provide an overview of the calpain superfamily and calpain-related disorders, assess the various emerging approaches for therapeutically targeting calpains and highlight agents currently in clinical trials.
Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targetsNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-04
Yufang Shi, Liming Du, Liangyu Lin, Ying Wang
Mesenchymal stem cells (MSCs) actively contribute to the formation of the tumour microenvironment by producing various factors that affect tumour growth and response to therapy. Moreover, MSCs can modulate tumour immunity. This Review discusses the various roles of MSCs in cancer and highlights potential strategies to target pro-tumorigenic activities of MSCs or take advantage of the tumour-homing capacity of MSCs for the delivery of drugs.
Phase II and phase III failures: 2013–2015Nat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-04
Richard K. Harrison
This article analyses recent data on the reported causes of drug candidate attrition, which indicate that lack of efficacy is the reason for approximately half of all phase II and phase III failures.
Defining the brain circuits involved in psychiatric disorders: IMI-NEWMEDSNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-04
Francesc Artigas, Esther Schenker, Pau Celada, Michael Spedding, Laia Lladó-Pelfort, Noemi Jurado, Mercedes Núñez, Noemi Santana, Eva Troyano-Rodriguez, Maurizio S. Riga, Hanna van den Munkhof, Anna Castañé, Hamdy Shaban, Thérèse M. Jay, Anushree Tripathi, Bill P. Godsil, Claude Sebban, Jean Mariani, Philippe Faure, Samir Takkilah, Zoe A. Hughes, Chester J. Siok, Mihaily Hajos, Karsten Wicke, Natalia Gass, Wolfgang Weber-Fahr, Alexander Sartorius, Robert Becker, Michael Didriksen, Jesper F. Bast
Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.
Antimicrobial drugs: Multifaceted approach to multidrug resistanceNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Multidrug-resistant (MDR) Gram-negative bacteria represent an increasing threat to public health, which is compounded by the dearth of drug candidates in the pipeline against such pathogens. Now, a study published in Nature Microbiology describes a new class of structurally nanoengineered antimicrobial peptide polymers (SNAPPs)
Autoimmune disease: CK2 blockade ameliorates EAENat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
T helper 17 (TH17) cells infiltrating the central nervous system are believed to have a crucial role in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Here, Ulges et al. report that genetic ablation or pharmacological blockade of the protein casein kinase 2
Lysosomal storage diseases: HSP70 reverses lysosomal pathologyNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Existing treatment options for the lysosomal storage diseases (LSDs) known as sphingolipidoses are limited and have little efficacy against neurological manifestations. Here, Kirkegaard et al. report that recombinant human heat shock protein 70 (HSP70) enhances binding of sphingolipid-degrading enzymes to their essential cofactor bis(monoacylglycero)phosphate
Anticancer agents: ACC inhibition suppresses lung cancerNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Targeting the elevated rate of de novo fatty acid synthesis (FASyn), which often occurs in tumour cells, has emerged as a promising therapeutic strategy. However, efforts to inhibit acetyl-CoA carboxylase (ACC) — the rate-limiting enzyme in FASyn — have so far been unsuccessful. Svensson
Malaria: Novel antimalarial target identifiedNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Current antimalarial strategies are limited by the complex life cycle of Plasmodium parasites and the emergence of drug-resistant strains. With these challenges in mind, Kato et al. screened a diverse panel of 100,000 compounds, which were produced using diversity-oriented synthesis (DOS), to identify
Anticancer drugs: Translating the undruggable targetNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Clear cell renal cell carcinoma (ccRCC) is largely attributable to inactivating mutations in the von Hippel−Lindau tumour suppressor pVHL, which drive accumulation and activation of the transcription factor hypoxia-inducible factor 2α (HIF2α). HIF2α, like many transcription factors, was considered undruggable until the discovery of a
HIV: Sequential vaccine elicits broadly neutralizing antibodiesNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Some (rare) HIV-infected individuals develop antibodies with broad and potent neutralizing activity (bnAbs). A vaccine that elicits such bnAbs is likely to be protective; however, the development of such a vaccine has proved to be exceptionally challenging. Now, two reports by Nussenzweig, Schief and colleagues
Hypertension: Purinergic receptor inhibition lowers blood pressureNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Hypertension is often poorly controlled by existing therapies owing, in part, to resistance to antihypertensive medications, poor compliance and side effects. Novel strategies to regulate blood pressure more effectively are therefore warranted. Writing in Nature Medicine, Pijacka and colleagues now report that inhibition of
Cancer: Closing the door on KRAS-mutant lung cancerNat. Rev. Drug. Disc ( IF 47.120 ) 2016-11-03
Despite considerable effort to target KRAS mutations, which are particularly common in pancreatic, colorectal and lung cancers, personalized therapies are not clinically available, and these cancers remain among the most lethal. A screen in non-small-cell lung cancer (NSCLC) cells has identified nuclear export proteins,
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