Drug discovery articles within Nature Communications

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  • Article |

    Small interfering RNA is degraded by plasma and can’t cross the cell membrane due to its negative charge. Here, the authors present an influenza inspired polymer carrier, capable of local RNA delivery, which degrades to a non-toxic by-product, and is thus suitable for multiple doses.

    • Nghia P Truong
    • , Wenyi Gu
    •  & Michael J Monteiro

  • Article |

    Large-scale screening of animal phenotypes requires automated detection and analysis of complex morphological information. Here, Yanik and colleagues present an imaging system based on optical projection tomography that generates micrometre-resolution 3D images of zebrafish larvae with within tens of seconds per animal.

    • Carlos Pardo-Martin
    • , Amin Allalou
    •  & Mehmet Fatih Yanik

  • Article |

    Cell-penetrating peptides can be used to deliver nucleic acids and proteins to cells, however they lack selectivity. In this study, cell-penetrating peptides are generated that can selectively target tumour cells of different cellular origins and these may be useful in the treatment of cancer.

    • Eisaku Kondo
    • , Ken Saito
    •  & Masayuki Matsushita

  • Article
    | Open Access

    Cachexia, or muscle-wasting syndrome, is often observed in patients with cancer or sepsis, and no specific treatment of cachexia is currently available. In this study, Di Marcoet al.show that low doses of pateamine A, an inhibitor of translation initiation, prevent cachexia in a mouse model of the disease.

    • Sergio Di Marco
    • , Anne Cammas
    •  & Imed Eddine Gallouzi

  • Article |

    Metformin is used to treat diabetes and its use has been associated with reduced cancer incidence, but the mechanism is unclear. In this study, metformin is shown to alter microRNA expression including an increase in mir-33a, which decreases the expression of the oncogenec-Myc.

    • Giovanni Blandino
    • , Mariacristina Valerio
    •  & Sabrina Strano

  • Article
    | Open Access

    Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.

    • Matthew Campbell
    • , Finnian Hanrahan
    •  & Peter Humphries

  • Article
    | Open Access

    Phage display screening can unravel protein–protein interactions, but its application has been mainly restricted to the cell surface. Here, a phage-based reagent is introduced that allows the targeting of combinatorial peptides to cell organelles, providing a tool for the discovery of intracellular ligand-receptors.

    • Roberto Rangel
    • , Liliana Guzman-Rojas
    •  & Wadih Arap

  • Article
    | Open Access

    Lung injury initiates a series of wound-healing responses, which if unregulated, can lead to fibrosis. Liet al. show that the deubquitinase CYLD has a key role in the prevention of fibrosis by inhibiting transforming growth factor β-signalling through the direct deubiquitination of the protein kinase Akt.

    • Jae Hyang Lim
    • , Hirofumi Jono
    •  & Jian-Dong Li

  • Article |

    Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.

    • Tarun Kumar Bhatt
    • , Sameena Khan
    •  & Amit Sharma

  • Article
    | Open Access

    Group-1 influenza A neuramidase proteins have a 150-cavity that can be targeted by drugs, but the 2009 H1N1 virus neuramidase is not thought to have a 150-cavity. Here, biophysical simulations show that the 2009 H1N1 neuramidase exists in solution with an open 150-cavity, which is stabilized by a salt bridge.

    • Rommie E. Amaro
    • , Robert V. Swift
    •  & Robin M. Bush

  • Article |

    The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.

    • Yasushi Ogawa
    • , Yosuke Nonaka
    •  & Masatoshi Hagiwara

  • Review Article |

    Biologically active molecules can be identified through the screening of small-molecule libraries, but compound collections typically consist of large numbers of structurally similar compounds. Gallowayet al. review how diversity-oriented synthesis can efficiently generate structurally diverse compound libraries.

    • Warren R.J.D. Galloway
    • , Albert Isidro-Llobet
    •  & David R. Spring

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