Featured
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News & Views |
Blueprints for ATP machinery will aid tuberculosis drug design
Structural insights into how anti-tuberculosis drugs interact with the enzyme that makes ATP in bacteria and humans pave the way for improved drug design to treat the disease and combat antimicrobial resistance.
- Gregory M. Cook
- & Matthew B. McNeil
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Article |
A µ-opioid receptor modulator that works cooperatively with naloxone
A newly discovered negative allosteric modulator of the µ-opioid receptor works together with naloxone to potently block opioid agonist signalling with reduced adverse effects.
- Evan S. O’Brien
- , Vipin Ashok Rangari
- & Brian K. Kobilka
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Article |
Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587
Cryogenic electron microscopy structures of Mycobacterium tuberculosis ATP synthase and human ATP synthase bound to the anti-tuberculosis drug bedaquiline or its analogue TBAJ-587 shed light on drug binding and could lead to new treatments for tuberculosis.
- Yuying Zhang
- , Yuezheng Lai
- & Hongri Gong
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News |
Ketamine for depression: slow-release pills could make treatment more accessible
A ketamine-containing tablet could be a convenient alternative to intravenous treatments, with fewer unpleasant side effects.
- Helena Kudiabor
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News |
These 3D model brains with cells from several people are first of their kind
Chimeric brain ‘organoids’ promise to help reveal individual variation in brain development and in drug responses.
- Asher Mullard
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News |
Cheaper versions of blockbuster obesity drugs are being created in India and China
As the patents on various weight-loss drugs near expiry, companies in India and China are vying to make lower-cost versions that will widen access to such treatments.
- Smriti Mallapaty
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News |
Unease as US drug agency weighs its use of independent scientists
After several controversial drug approvals, the US Food and Drug Administration is mulling over changes to its advisory panels, which include researchers and others.
- Max Kozlov
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Editorial |
CRISPR cures and cancer vaccines: researchers can help to shepherd them to market
It’s not just people with ultra-rare disorders who could benefit from hyper-personalized therapies. Scientists and regulators must work together to ensure the benefits are spread.
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Research Highlight |
AI finds huge cache of anti-bacterial peptides hidden in genomic data
Machine-learning technique uncovers nearly 900,000 microbe-fighting peptide sequences in genomes collected from soils and other sources.
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Outlook |
Randomized trials of cancer drugs are for yesterday
Pitting new treatments against old, ineffective agents is neither ethical nor economical.
- Elaine Schattner
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Outlook |
How antibody–drug conjugates aim to take down cancer
Scientists are trying to work out how to balance potency with toxicity and tackle the cost of next-generation therapeutics.
- Benjamin Plackett
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Outlook |
Natural killer cells show their cancer-fighting worth
Although natural-killer-cell therapies are safer than T-cell therapies and offer other advantages, they require upgrades to overcome their limited lifespan and susceptibility to immunosuppression.
- Amanda B. Keener
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News |
‘Smart’ antibiotic can kill deadly bacteria while sparing the microbiome
Compound called lolamicin targets a group of harmful microbes but does not disturb those that live peacefully in the gut.
- Fred Schwaller
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Editorial |
AlphaFold3 — why did Nature publish it without its code?
Criticism of our decision to publish AlphaFold3 raises important questions. We welcome readers’ views.
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Article |
Bitter taste TAS2R14 activation by intracellular tastants and cholesterol
A cryogenic electron microcopy study of structures of a human receptor for bitter taste finds that cholesterol can activate the receptor, while the tastant molecule acts allosterically on the receptor.
- Xiaolong Hu
- , Weizhen Ao
- & Zhi-Jie Liu
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News & Views |
Dual-action obesity drug rewires brain circuits for appetite
A two-in-one drug that modulates neural pathways involved in appetite and reward might prove to be more effective and longer lasting than current weight-loss drugs on the market.
- Tyler M. Cook
- & Darleen Sandoval
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News |
Experimental obesity drug packs double punch to reduce weight
Test of weight-loss candidate in mice shows that there is still room for improvement in a burgeoning field.
- Asher Mullard
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News Feature |
How to kill the ‘zombie’ cells that make you age
Researchers are using new molecules, engineered immune cells and gene therapy to kill senescent cells and treat age-related diseases.
- Carissa Wong
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Article
| Open AccessGLP-1-directed NMDA receptor antagonism for obesity treatment
Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.
- Jonas Petersen
- , Mette Q. Ludwig
- & Christoffer Clemmensen
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Research Briefing |
Toad psychedelic points to biological target for antidepressants
A hallucinogenic compound secreted by toads has served as a springboard for research into the therapeutic benefits of psychedelics. The findings suggest that these compounds exert antidepressant effects in part by binding an under-appreciated target in the brain.
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News |
Major AlphaFold upgrade offers boost for drug discovery
Latest version of the AI models how proteins interact with other molecules — but DeepMind restricts access to the tool.
- Ewen Callaway
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Article
| Open AccessAccurate structure prediction of biomolecular interactions with AlphaFold 3
AlphaFold 3 has a substantially updated architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues with greatly improved accuracy over many previous specialized tools.
- Josh Abramson
- , Jonas Adler
- & John M. Jumper
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Article
| Open AccessDiscovery of potent small-molecule inhibitors of lipoprotein(a) formation
Biochemical screening and optimization identify small molecules that inhibit the formation of lipoprotein(a), and these inhibitors reduce the levels of Lp(a) in several animal models, suggesting that they could provide a therapeutic option in humans.
- Nuria Diaz
- , Carlos Perez
- & Laura F. Michael
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News |
UTIs make life miserable — scientists are finding new ways to tackle them
Researchers are developing vaccines and fresh drug approaches to prevent and treat recurring infections without antibiotics.
- Carissa Wong
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Arts Review |
Las Borinqueñas remembers the forgotten Puerto Rican women who tested the first pill
Clinical trials of the first oral contraceptive recalled in a bold theatre production.
- Mariana Lenharo
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News Explainer |
Plastic pollution: three numbers that support a crackdown
As negotiators haggle over a global treaty to curb plastics pollution, a flood of data outlines how a treaty could make a difference.
- Nicola Jones
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Analysis
| Open AccessRefining the impact of genetic evidence on clinical success
Human genetic evidence increases the success rate of drugs from clinical development to approval but we are still far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.
- Eric Vallabh Minikel
- , Jeffery L. Painter
- & Matthew R. Nelson
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News Feature |
Obesity drugs aren’t always forever. What happens when you quit?
Many researchers think that Wegovy and Ozempic should be taken for life, but myriad factors can force people off them.
- McKenzie Prillaman
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Article |
Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids
Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.
- Jean-Philippe Auger
- , Max Zimmermann
- & Gerhard Krönke
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Article |
Bitter taste receptor activation by cholesterol and an intracellular tastant
Cryo-electron microscopy structures of the type 2 taste receptor TAS2R14 in complex with Ggust and Gi1 identify cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator and agonist.
- Yoojoong Kim
- , Ryan H. Gumpper
- & Bryan L. Roth
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Comment |
AI can help to tailor drugs for Africa — but Africans should lead the way
Computational models that require very little data could transform biomedical and drug development research in Africa, as long as infrastructure, trained staff and secure databases are available.
- Gemma Turon
- , Mathew Njoroge
- & Kelly Chibale
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Article
| Open AccessTumour-selective activity of RAS-GTP inhibition in pancreatic cancer
RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.
- Urszula N. Wasko
- , Jingjing Jiang
- & Kenneth P. Olive
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News |
‘A landmark moment’: scientists use AI to design antibodies from scratch
Modified protein-design tool could make it easier to tackle challenging drug targets — but AI antibodies are still a long way from reaching the clinic.
- Ewen Callaway
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Nature Index |
A spotlight on the stark imbalances of global health research
An expansion of the Nature Index to include more than 60 medical journals has revealed the clear leaders in the field.
- Bec Crew
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News Feature |
Can non-profits beat antibiotic resistance and soaring drug costs?
Effective, affordable antimicrobial drugs aren’t moneymakers, despite being desperately needed. Can non-profit organizations pick up the slack?
- Maryn McKenna
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Article
| Open AccessAnti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells
A high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients with non-small cell lung cancer treated with atezolizumab plus tiragolumab, but not with atezolizumab alone.
- Xiangnan Guan
- , Ruozhen Hu
- & Namrata S. Patil
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Technology Feature |
How phase separation is revolutionizing biology
Imaging and molecular manipulation reveal how biomolecular condensates form and offer clues to the role of phase separation in health and disease.
- Elie Dolgin
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News Explainer |
‘Breakthrough’ allergy drug: injection protects against severe food reactions
A study suggests that the asthma treatment omalizumab can reduce the risk of dangerous allergic reactions to peanuts and other foods.
- Sara Reardon
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News |
Drug-resistant microbes: ‘brain drain’ is derailing the fight to stop them
A lack of investment is driving researchers who study antimicrobial resistance out of the field, an industry body warns.
- Lilly Tozer
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News |
Mirror-image molecules separated using workhorse of chemistry
The ability to distinguish between left- and right-handed molecules using mass spectrometry could streamline a laborious part of drug discovery.
- Katharine Sanderson
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Correspondence |
Clinical trials: Japan’s opt-out policy raises risks of adverse drug responses
- Mira Namba
- , Yudai Kaneda
- & Tetsuya Tanimoto
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Comment |
Forget lung, breast or prostate cancer: why tumour naming needs to change
The conventional way of classifying metastatic cancers according to their organ of origin is denying people access to drugs that could help them.
- Fabrice André
- , Elie Rassy
- & Benjamin Besse
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News |
AlphaFold found thousands of possible psychedelics. Will its predictions help drug discovery?
Researchers have doubted how useful the AI protein-structure tool will be in discovering medicines — now they are learning how to deploy it effectively.
- Ewen Callaway
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News & Views |
A new type of antibiotic targets a drug-resistant bacterium
Infections caused by drug-resistant strains of the bacterium Acinetobacter baumannii have been hard to treat in the clinic. A new class of antibiotics has been identified with the potential to tackle these microbes.
- Morgan K. Gugger
- & Paul J. Hergenrother
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Article
| Open AccessA novel antibiotic class targeting the lipopolysaccharide transporter
A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB2FGC complex.
- Claudia Zampaloni
- , Patrizio Mattei
- & Kenneth A. Bradley
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Research Briefing |
‘Explainable’ AI identifies a new class of antibiotics
An artificial-intelligence graph neural network was trained on experimental data and used to identify chemical substructures that underlie selective antibiotic activity in more than 12 million compounds. This led to the discovery of a class of antibiotics with in vitro and in vivo activity against Gram-positive bacteria, including Staphylococcus aureus.
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Article |
Discovery of a structural class of antibiotics with explainable deep learning
An explainable deep learning model using a chemical substructure-based approach for the exploration of chemical compound libraries identified structural classes of compounds with antibiotic activity and low toxicity.
- Felix Wong
- , Erica J. Zheng
- & James J. Collins
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Article
| Open AccessThe energetic and allosteric landscape for KRAS inhibition
Analysis of the effects of more than 26,000 KRAS mutations on abundance and interactions with six other proteins is used to construct an energy landscape of KRAS and identify allosteric drug target sites.
- Chenchun Weng
- , Andre J. Faure
- & Ben Lehner