Drug development articles within Nature Communications

Featured

  • Article
    | Open Access

    Bacteria-based therapy has shown promise for cancer treatment. To enhance tumor accumulation, here the authors describe the design of tumor specific aptamer-conjugated bacteria, to improve intratumor localization and enhance therapeutic efficacy.

    • Zhongmin Geng
    • , Zhenping Cao
    •  & Weihong Tan

  • Article
    | Open Access

    The toxicity arising from generalised stimulation of T cells restricts applicability of CD137 agonists in cancer immune therapy. Here authors show that a bispecific antibody blocking PD-1 while activating CD137 efficiently restricts T cell activation to the tumour microenvironment, resulting in efficient tumour control and reduced liver toxicity.

    • Yunqian Qiao
    • , Yangmin Qiu
    •  & Xuan Wang

  • Article
    | Open Access

    Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.

    • Weier Bao
    • , Ming Liu
    •  & Zhiyuan Tian

  • Article
    | Open Access

    Berberine is a compound with glucose-lowering effects in mice and humans. Here, the authors show that in mice berberine has beneficial glycemic effects by promoting insulin secretion, which requires the potassium channel KCNH6 in beta cells, and that berberine can promote insulin secretion in healthy men in a phase 1 clinical trial.

    • Miao-Miao Zhao
    • , Jing Lu
    •  & Jin-Kui Yang

  • Article
    | Open Access

    Improved therapeutic strategies are needed as drug resistance limits the therapeutic efficacy of several clinically approved cancer therapeutics. Here, the authors report a ferroptosis-based therapy using a combination of iron nanoparticles with gene interference to knockdown iron metabolic genes, FPN and LCN2.

    • Jinliang Gao
    • , Tao Luo
    •  & Jinke Wang

  • Article
    | Open Access

    Heart failure is a major cause of morbidity and mortality worldwide. Here the authors show that subcutaneous administration of antisense oligonucleotides targeting PLN is an effective strategy in preclinical models of genetic cardiomyopathy and ischemia-driven heart failure.

    • Niels Grote Beverborg
    • , Daniela Später
    •  & Peter van der Meer

  • Article
    | Open Access

    Proteomics can aid in the identification of molecular subtypes in cancers. Here, the authors perform proteomic profiling of 124 paired oesophageal cancer and adjacent non-tumour tissues and identify two subtypes that are associated with patient survival for therapeutic targeting.

    • Wei Liu
    • , Lei Xie
    •  & En-Min Li

  • Article
    | Open Access

    Restoring oxygenation in hypoxic tumors might lead to favorable oncological outcome of patients if combined with standard multimodal therapy regimens. Here the authors report a phase Ib clinical trial of anti-hypoxic myo-inositol trispyrophosphate (ITPP) in hepato-pancreato-biliary neoplasms.

    • Marcel A. Schneider
    • , Michael Linecker
    •  & Perparim Limani

  • Article
    | Open Access

    Molecular dynamics (MD) techniques enable atomic-level observations, but simulations of “slow” biomolecular processes are challenging because of current computer speed limitations. Here, the authors develop a method to accelerate MD simulations by high-frequency ultrasound perturbation and reveal binding events between the protein CDK2 and its small-molecule inhibitors.

    • Mitsugu Araki
    • , Shigeyuki Matsumoto
    •  & Yasushi Okuno

  • Article
    | Open Access

    There are few treatments for male infertility. Here, the authors show that the receptor activator of NF-κB ligand (RANKL) signalling pathway has important functions in sperm production and maturation, improves fertility in male mice and shows potential as a male infertility target.

    • Martin Blomberg Jensen
    • , Christine Hjorth Andreassen
    •  & Anders Juul

  • Article
    | Open Access

    HCCAA is a dominantly inherited disease which causes brain hemorrhages as a result of mutant cystatin C aggregation in carriers. Here, the authors show that n- acetyl cysteine can prevent aggregation of mutant protein in a cell model system and reverse protein deposition in the skin of mutation-carrying subjects.

    • Michael E. March
    • , Alvaro Gutierrez-Uzquiza
    •  & Hakon Hakonarson

  • Article
    | Open Access

    Favipiravir has broad-spectrum antiviral activity against a variety of RNA viruses. Here the authors investigate the safety, pharmacokinetics and anti-SARS-CoV-2 efficacy of different drug dosage in the a Syrian hamster model of infection and, combined with genetic analyses, they show that Favipiravir at high doses decrease viral infectivity while inducing the emergence of mutations in viral genomes, decreasing fitness.

    • Jean-Sélim Driouich
    • , Maxime Cochin
    •  & Antoine Nougairède

  • Article
    | Open Access

    Drug response in cancer patients vary dramatically due to inter- and intra-tumor heterogeneity and transcriptome context plays a significant role in shaping the actual treatment outcome. Here, the authors develop a deep variational autoencoder model to compress gene signatures into latent vectors and accurately impute drug response.

    • Peilin Jia
    • , Ruifeng Hu
    •  & Zhongming Zhao

  • Article
    | Open Access

    It is challenging to map complex processes in brain tissue. Here the authors report a toolkit enabling large-scale multiplexed IHC and automated cell classification whereby they use a conventional epifluorescence microscope and deep neural networks to phenotype all major cell classes of the brain.

    • Dragan Maric
    • , Jahandar Jahanipour
    •  & Badrinath Roysam

  • Article
    | Open Access

    Resistance to ALK inhibitors such as lorlatinib often arise due to on-target mutations. Here, the authors show the multi-kinase inhibitor gilteritinib is effective against different mutations that arise during lorlatinib in ALK fusion positive lung cancer to cause resistance.

    • Hayato Mizuta
    • , Koutaroh Okada
    •  & Ryohei Katayama

  • Article
    | Open Access

    In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

    • Jiaojiao Pang
    • , Feng Xu
    •  & Yihai Cao

  • Article
    | Open Access

    Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, the authors report an efficient network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of human cerebral organoids.

    • Jong-Chan Park
    • , So-Yeong Jang
    •  & Inhee Mook-Jung

  • Article
    | Open Access

    Cellular senescence is a hallmark of ageing and is important for the pathogenesis of ageing-related diseases. Here, the authors develop a morphology-based deep learning system to identify senescent cells and a quantitative scoring system to evaluate the state of endothelial cells to evaluate the effects of anti-senescent reagents.

    • Dai Kusumoto
    • , Tomohisa Seki
    •  & Shinsuke Yuasa

  • Article
    | Open Access

    Histones, proteins that bind DNA, are toxic for pathogens outside cells but can also cause multi-organ damage as seen in sepsis. Here the authors develop small negatively charged molecules that can be used as histone antidotes, and show that they improve the phenotype in mouse models with histone-related pathologies.

    • Connor H. O’ Meara
    • , Lucy A. Coupland
    •  & Christopher R. Parish

  • Article
    | Open Access

    Nonalcoholic steatohepatitis (NASH) and associated liver fibrosis have limited therapy options. Here the authors report a novel adiponectin-based dual agonist for adiponectin receptors 1 and 2 with a longer half-life, and show that it ameliorates NASH and liver fibrosis in mouse models.

    • Hongjiao Xu
    • , Qian Zhao
    •  & Xianxing Jiang

  • Article
    | Open Access

    Testis-restricted melanoma antigen (MAGE) proteins function as substrate adapters for E3 ubiquitin ligases. Biochemical and structural analyses of MAGE-A11 provide insight into the substrate binding mode of MAGE proteins and enable discovery of potent, cytotoxic inhibitors of MAGE-A11:substrate interaction.

    • Seung Wook Yang
    • , Xin Huang
    •  & Patrick Ryan Potts

  • Article
    | Open Access

    Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here, the authors generate single-drug nanoparticles by hybridising lysomotropic detergents and the bisaminoquinoline-based autophagy inhibitor, and show their therapeutic potential as autophagy-inhibition based combination therapy.

    • Zhao Ma
    • , Jin Li
    •  & Yuanpei Li

  • Article
    | Open Access

    TMBIM6, a member of the transmembrane BI-1 motif-containing family of proteins, is overexpressed in many cancer types. Here, the authors show that TMBIM6 regulates AKT activation through mTORC2 assembly and ribosome association and identify an antagonist of TMBIM6 with anti-tumor properties.

    • Hyun-Kyoung Kim
    • , Kashi Raj Bhattarai
    •  & Han-Jung Chae

  • Article
    | Open Access

    Mendelian randomisation (MR) analysis of drug targets has potential to aid drug development. Here, the authors introduce a mathematical framework to elucidate this specific application of MR.

    • Amand F. Schmidt
    • , Chris Finan
    •  & Aroon D. Hingorani

  • Article
    | Open Access

    The clinical application of T cell bispecific antibodies (TCBs) is often limited by the lack of tumour-specific antigens. In this study, the authors present a strategy to increase TCB tumour-selectivity by adding an anti-CD3 moiety that can be specifically activated by tumor specific proteases in the tumor microenvironment.

    • Martina Geiger
    • , Kay-Gunnar Stubenrauch
    •  & Christian Klein

  • Article
    | Open Access

    Phosphodiesterase-5 (PDE5) inhibitors have been suggested to have an anti-tumor effect and block surgery-induced immunosuppression. Here, the authors show that postdiagnostic use of PDE5 inhibitors is associated with a decreased risk of colorectal cancerspecific mortality as well as a decreased risk of metastasis.

    • Wuqing Huang
    • , Jan Sundquist
    •  & Jianguang Ji

  • Article
    | Open Access

    Inhibitors of the BET family proteins are limited by their potency and oral bio-availability. Here, the authors report a new BET inhibitor, NHWD-870, with improved potency compared to previous BET inhibitors, and show that it suppresses BRD4 and targets tumour associated macrophages.

    • Mingzhu Yin
    • , Ying Guo
    •  & Qin Yan

  • Article
    | Open Access

    The serotonin transporter (SERT) terminates serotonin signaling and its activity is modulated by antidepressants. Here authors reveal the mechanistic details underlying the coupling between the two binding sites in SERT and a high-affinity ligand for the allosteric site.

    • Per Plenge
    • , Ara M. Abramyan
    •  & Claus J. Loland

  • Article
    | Open Access

    Inhibition of PERK, an endoplasmic reticulum (ER) unfolded protein response (UPR) protein, is a potential pharmacological target for cancer treatment. Here, the authors show that inhibition of PERK under ER stress affects trafficking from the ER to the surface of several key receptor tyrosine kinases, suggesting a selective ER retention.

    • Mohamed Mahameed
    • , Shatha Boukeileh
    •  & Boaz Tirosh

  • Article
    | Open Access

    Although paclitaxel is widely used as a chemotherapy, it suffers from poor solubility and toxicity issues. Here, the authors develop thermostable RNA nanoparticles and report the RNA-paclitaxel complex to display improved stability, drug loading capacity and solubility for improved targeted cancer therapy and reduced immune responses.

    • Sijin Guo
    • , Mario Vieweger
    •  & Peixuan Guo

  • Article
    | Open Access

    Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.

    • Timothy P. Sheahan
    • , Amy C. Sims
    •  & Ralph S. Baric

  • Article
    | Open Access

    Cancer therapy using oncolytic virus has shown pre-clinical and clinical efficacy. Here, the authors report ExtraCRAd, an oncolytic virus cloaked with tumour cell membrane and report its therapeutic effects in vitro and in vivo in multiple mouse tumour models.

    • Manlio Fusciello
    • , Flavia Fontana
    •  & Vincenzo Cerullo

  • Article
    | Open Access

    The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.

    • Tamer S. Kaoud
    • , William H. Johnson
    •  & Kevin N. Dalby

  • Article
    | Open Access

    Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

    • Nadine D. Arnold
    • , Josephine A. Pickworth
    •  & Allan Lawrie

  • Article
    | Open Access

    The build-up of iron in the body can have serious consequences; current treatment therapies suffer from adverse side effects and toxicity. Here, the authors developed renal clearable nanochelators with improved pharmacodynamics and demonstrated their efficacy and safety in iron overload animal models.

    • Homan Kang
    • , Murui Han
    •  & Jonghan Kim

  • Article
    | Open Access

    DNA-dependent protein kinase (DNA-PK) plays a major role in the DNA damage response upon double-strand break formation. Here, the authors show that the DNA-PK inhibitor AZD7648, enhances the activity of radiotherapy, chemotherapy and the PARP inhibitor olaparib in multiple mouse tumour models.

    • Jacqueline H. L. Fok
    • , Antonio Ramos-Montoya
    •  & Elaine B. Cadogan

  • Article
    | Open Access

    Senolytic compounds have the ability to eliminate senescent cells from tissues and have been shown to be beneficial in various animal models of age-related diseases. Here the authors show that cardiac glycosides commonly used for heart diseases have senolytic properties in humanized mouse models of tumorigenesis and lung fibrosis.

    • Francisco Triana-Martínez
    • , Pilar Picallos-Rabina
    •  & Manuel Collado

  • Article
    | Open Access

    PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.

    • Wen Zhang
    • , Georgios Voloudakis
    •  & Panos Roussos

  • Article
    | Open Access

    The limited efficacy of current immunotherapy suggests low antigen-specific T cells and immunosuppressive factors in tumor microenvironment (TME). Here, the authors develop a syringeable immunomodulatory multi-domain nanogel that can reprogram the TME and induce enhanced cancer immunotherapy.

    • Chanyoung Song
    • , Hathaichanok Phuengkham
    •  & Yong Taik Lim

  • Article
    | Open Access

    Antivenoms, obtained by venom immunization, have narrow species coverage due to low immunogenicity of venom neurotoxins. Here the authors immunize horses with a designed recombinant consensus neurotoxin, and the resulting antisera protect mice from envenomation by a broad spectrum of elapid snakes.

    • Guillermo de la Rosa
    • , Felipe Olvera
    •  & Gerardo Corzo

  • Article
    | Open Access

    Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate determining step for NAD+ synthesis and is of interest as a drug target. Here the authors identify and characterize a small molecule NAMPT activator SBI-797812, elucidate its mode of action and show that it increases intracellular NMN and NAD+ levels in cultured cells and elevates liver NAD+ in mice.

    • Stephen J. Gardell
    • , Meghan Hopf
    •  & Anthony B. Pinkerton

  • Article
    | Open Access

    Cryptosporidium infection can cause severe diarrhea with limited treatment options available. Here, Lunde et al. perform a drug repositioning screen with a library of benzoxaboroles and identify AN7973 as potent inhibitor of intracellular parasite development with good efficacy in murine and neonatal dairy calf disease models.

    • Christopher S. Lunde
    • , Erin E. Stebbins
    •  & Christopher D. Huston

  • Article
    | Open Access

    Phosphatase of regenerating liver 3 (PRL3) is usually found intracellularly, and is over-expressed in cancer cells. Here the authors show that PRL-3 is also detectable on cell surface, and can be recognized by PRL3-zumab to recruit immune cells into tumor to promote anti-tumor immunity, thereby implicating PRL-3 as a potential tumor antigen.

    • Min Thura
    • , Abdul Qader Al-Aidaroos
    •  & Qi Zeng

  • Article
    | Open Access

    Cells of the pulmonary vasculature show a hyperproliferative phenotype in pulmonary arterial hypertension (PAH), thus contributing to the disease pathogenesis. Here the authors show that cyclin-dependent kinases are overactivated in PAH, and that their pharmacological inhibition attenuates the disease in two independent rodent models

    • Astrid Weiss
    • , Moritz Christian Neubauer
    •  & Ralph Theo Schermuly

  • Article
    | Open Access

    Here, the authors develop a mouse model of Loa loa that reflects human infections, including eosinophilia, and determine effects of ivermectin treatment.

    • Nicolas P. Pionnier
    • , Hanna Sjoberg
    •  & Joseph D. Turner

Browse broader subjects

Browse Drug development across other nature.com journals