Article
|
Open Access
Featured
-
-
Article
| Open AccessPredicting crystal form stability under real-world conditions
Accuracy of free-energy calculations can be improved by constructing an experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate and anhydrate crystal structures on the same energy landscape.
- Dzmitry Firaha
- , Yifei Michelle Liu
- & Marcus A. Neumann
-
Article |
Carbon-to-nitrogen single-atom transmutation of azaarenes
A new type of transformation converting a heteroaromatic carbon atom into a nitrogen atom, turning quinolines into quinazolines to enable manipulation of molecular properties, is reported.
- Jisoo Woo
- , Colin Stein
- & Mark D. Levin
-
Article |
Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane
The potential power of the saturated carbocycle bicyclo[3.1.1]heptane as a beneficial motif for improving the pharmacokinetic and physicochemical properties of drug candidates is demonstrated.
- Nils Frank
- , Jeremy Nugent
- & Edward A. Anderson
-
Article |
Rational design of a new antibiotic class for drug-resistant infections
A lead-optimization strategy combining porin permeation properties and biochemical potency leads to development of a new class of antibiotic based on broad inhibition of penicillin-binding proteins from Gram-negative bacteria.
- Thomas F. Durand-Reville
- , Alita A. Miller
- & Ruben A. Tommasi
-
Article |
RETRACTED ARTICLE: IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance
A class of compounds with a dual mechanism of action—direct targeting of IspH and stimulation of cytotoxic γδ T cells to enhance pathogen clearance—are active against multidrug-resistant bacteria.
- Kumar Sachin Singh
- , Rishabh Sharma
- & Farokh Dotiwala
-
Article |
Synthetic group A streptogramin antibiotics that overcome Vat resistance
Modular synthesis and structural biology are used to design and characterize group A streptogramin antibiotics, one of which has activity against streptogramin-resistant strains and demonstrates efficacy in a mouse model of bacterial infection.
- Qi Li
- , Jenna Pellegrino
- & Ian B. Seiple
-
Article |
Clinical targeting of HIV capsid protein with a long-acting small molecule
The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.
- John O. Link
- , Martin S. Rhee
- & Tomas Cihlar
-
Article |
Preparation of cyclohexene isotopologues and stereoisotopomers from benzene
Cyclohexene isotopologues and stereoisotopomers with varying degrees of deuteration are formed by binding a tungsten complex to benzene, which facilitates the selective incorporation of deuterium into any position on the ring.
- Jacob A. Smith
- , Katy B. Wilson
- & W. Dean Harman
-
Article |
Late-stage oxidative C(sp3)–H methylation
A manganese-catalysed oxidative C(sp3)–H methylation method allows a methyl group to be selectively installed into medicinally important heterocycles, providing a way to improve pharmaceuticals and better understand the ‘magic methyl effect’.
- Kaibo Feng
- , Raundi E. Quevedo
- & M. Christina White
-
Letter |
Nanoscale synthesis and affinity ranking
A system that combines nanoscale synthesis and affinity ranking enables high-throughput screening of reaction conditions and bioactivity for a given protein target, accelerating the process of drug discovery.
- Nathan J. Gesmundo
- , Bérengère Sauvagnat
- & Tim Cernak
-
Article |
Molecular basis of USP7 inhibition by selective small-molecule inhibitors
Small molecules are identified that inhibit the ubiquitin-specific protease USP7 with high affinity and specificity as explained by co-crystal structures, and are shown to reduce tumour growth in mice.
- Andrew P. Turnbull
- , Stephanos Ioannidis
- & David Komander
-
Letter |
Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure
The authors report the crystal structure of the β2 adrenergic receptor in complex with compound 15, an allosteric modulator that binds to an alternative binding pocket.
- Xiangyu Liu
- , Seungkirl Ahn
- & Brian K. Kobilka
-
Career Brief |
Big pharma: UK drugs outsourced
United Kingdom has cut drug-development research jobs over past decade.
-
-
Outlook |
Tropical disease: A neglected cause
A more open approach to combating tropical diseases may help to overcome a pharmaceutical market failure.
- Lucas Laursen
-
Outlook |
Q&A: Bernard Munos
In 2006, pharmaceutical innovation consultant Bernard Munos helped to launch a lively public discussion about how open innovation can bring novel drugs to market with his paper 'Can opensource R&D reinvigorate drug research? He tells Nature how things have changed since then.
- Eric Bender
-
Outlook |
A new chapter in innovation
A growing appreciation that cooperation and competition can coexist is transforming the life-sciences innovation landscape. Development was once shrouded in secrecy, but now organizations are coming together.
- David Holmes
-
Outlook |
Perspective: Science is still too closed
Open initiatives are promising, but we have much further to go if research data are to be as publicly accessible as they should be, says Aled Edwards.
- Aled Edwards
-
Outlook |
Competition: Unlikely partnerships
Drug discovery is time-consuming and full of blind alleys. Pharmaceutical rivals are cooperating in the early stages to accelerate and improve the efficiency of the process.
- Neil Savage
-
Outlook |
Chemical probes: A shared toolbox
In a pioneering move, the compound JQ1 was released to the community for free. The impact that this has had on research and development is slowly coming into focus.
- Andrew R. Scott
-
Outlook |
Challenges: Crowdsourced solutions
Open competitions bring new minds, skills and collaborations to problems in biomedical research.
- Eric Bender
-
Outlook |
Compound screening: Fresh hunting ground
In the search for novel therapies, drug developers have begun crowdsourcing molecules.
- Annabel McGilvray
-
Inside View |
Inside View: Astrazeneca
-
Article |
A novel multiple-stage antimalarial agent that inhibits protein synthesis
The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission.
- Beatriz Baragaña
- , Irene Hallyburton
- & Ian H. Gilbert
-
Outlook |
Clinical trials: More trials, fewer tribulations
Clinical studies that group patients according to their molecular profile can make for better and faster drug approval decisions.
- Michael Eisenstein
-
Article |
Automated design of ligands to polypharmacological profiles
An automated approach designing drug ligands to multi-target profiles (with a 75% prediction success rate) is experimentally validated by the invention of novel ligands tailored to the complex and physiologically-relevant goal of identifying drugs that can specifically target profiles of multiple proteins.
- Jérémy Besnard
- , Gian Filippo Ruda
- & Andrew L. Hopkins
-
News & Views |
Toolkit of reagents to aid drug discovery
Reagents have been developed that allow carbon—hydrogen bonds on benzene-like compounds called heterocycles to be converted directly into carbon—carbon bonds. The finding will be a boon to medicinal chemists. See Letter p.95
- William J. Pitts
-
Research Highlights |
Fragile-X drug in humans and mice
-
Outlook |
Therapeutics: Strength in numbers
Several new drugs for treating chronic obstructive pulmonary disease are about to hit the market, with more in the pipeline.
- Duncan Graham-Rowe
-
News |
Alzheimer’s drugs take a new tack
Hopes pinned on pre-emptive clinical trials after latest setbacks.
- Ewen Callaway
-
Editorial |
Take a stand
Legal actions and oversight are necessary to keep the drug industry in line.
-
Letter |
Activation of remote meta-C–H bonds assisted by an end-on template
Rapid synthesis of complex molecules via selective functionalization of unactivated carbon–hydrogen bonds is here made easier with the use of removable ‘templates’ that enable the activation of distal bonds.
- Dasheng Leow
- , Gang Li
- & Jin-Quan Yu
-
News |
Model pigs face messy path
As approvals for engineered food animals stall, pigs may be US regulators’ next challenge.
- Amy Maxmen
-
-
Feature |
Pharmaceutical sector: Delicate transition
With lay-offs rife in the drug industry, life scientists and chemists are seeking fresh career paths.
- Charlotte Schubert
-
Article |
Large-scale prediction and testing of drug activity on side-effect targets
A large-scale computational effort is used to predict the activity of 656 drugs against 73 protein targets that have been associated with adverse drug reactions; the abdominal pain side effect of the synthetic oestrogen chlorotrianisene is shown to be mediated through its inhibition of cyclooxygenase-1.
- Eugen Lounkine
- , Michael J. Keiser
- & Laszlo Urban
-
News & Views |
A breach in the blood–brain barrier
Alterations in brain blood vessels in mice precede the neural dysfunction associated with Alzheimer's disease. The finding highlights potential targets for drug development. See Letter p.512
- Peter Carmeliet
- & Bart De Strooper
-
Letter |
Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic
The crystal structure of the human nociceptin/orphanin FQ peptide receptor in complex with the peptide mimetic antagonist compound-24 is determined, with potential importance for the development of new therapeutic agents.
- Aaron A. Thompson
- , Wei Liu
- & Raymond C. Stevens
-
Letter |
Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’
Although IL-2 has been studied for its immune-stimulating activity against metastatic cancer, its side effects have limited its clinical use; here, an engineered IL-2 ‘superkine’ is shown to have increased activity, particularly in inducing antitumour T cells, but fewer side effects.
- Aron M. Levin
- , Darren L. Bates
- & K. Christopher Garcia
-
News |
Drug bests cystic-fibrosis mutation
First treatment to tackle protein behind the disease wins approval — but only a small fraction of patients will benefit.
- Heidi Ledford
-
News & Views |
Drugs to awaken a paternal gene
Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value. See Letter p.185
- Arthur L. Beaudet
-
Outlook |
Modernization: One step at a time
The repertoire of traditional Chinese medicine could offer rich pickings for modern drug developers, but researchers must first define and test herbal concoctions.
- Zhiguo Xu
-
Letter |
T-cell differentiation factor CBF-β regulates HIV-1 Vif-mediated evasion of host restriction
CBF-β is shown to regulate the ability of HIV-1 to evade host restriction mediated by the deaminase APOBEC3.
- Wenyan Zhang
- , Juan Du
- & Xiao-Fang Yu
-
Letter |
Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis
A simple and mild strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes that acts via a radical-mediated mechanism and uses commercial photocatalysts.
- David A. Nagib
- & David W. C. MacMillan
-
News |
Blockbuster drug bows out
Pharmaceutical industry anxiously struggles to retool as Lipitor patent expires.
- Heidi Ledford
-
-
Outlook |
Translational research: The American way
The United States publishes more biomedical research papers than ever before, yet drug development is stagnating. Several new initiatives aim to turn this knowledge into new remedies.
- Amy Maxmen
-
Letter |
Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation
- Jang Hyun Choi
- , Alexander S. Banks
- & Patrick R. Griffin
-
News |
Alzheimer's disease genes aid the search for preventive drugs
Proposed trials of candidate drugs before symptoms appear offer hope of more effective treatments.
- David Cyranoski