Drug discovery articles within Nature

Featured

  • News |

    FDA's strengthened powers to assess drugs already on the market will soon be put to the test.

    • Heidi Ledford

  • News & Views |

    It is hard to predict how strongly a small molecule will bind to a protein, but this is a crucial goal of computer-aided drug discovery. A new approach models the forcible removal of molecules from a protein's active site.

    • William L. Jorgensen

  • Article |

    Here the 2.1 Å crystal structure of human immunodeficiency virus (HIV) Tat protein complexed with the positive transcription elongation factor P-TEFb is reported. This shows that Tat binding changes the structure of P-TEFb, which may suggest opportunities for developing inhibitors that block only the form of P-TEFb used by the virus.

    • Tahir H. Tahirov
    • , Nigar D. Babayeva
    •  & David H. Price

  • Article |

    Here, nearly 2 million compounds from GlaxoSmithKline's chemical library were screened for inhibitors of the malaria parasite Plasmodium falciparum, grown in red blood cells. Of these compounds, some 13,500 inhibited parasite growth, and more than 8,000 also showed potent activity against a multidrug resistant strain. The targets of these compounds were inferred through bioinformatic analysis, revealing several new mechanisms of antimalarial action.

    • Francisco-Javier Gamo
    • , Laura M. Sanz
    •  & Jose F. Garcia-Bustos

  • Editorial |

    The United States should protect investments used to find new uses for old drugs.

  • Column |

    Is Bill Gates's decision to invest in software company Schrödinger an early sign of a new computer-aided era for drug design, asks Derek Lowe. Or is it just another small step on what's been a rather lengthy journey?

    • Derek Lowe

  • News & Views |

    Infection with hepatitis C is one of the main causes of liver disease, yet there are no broadly effective treatments. Discovery of a potent inhibitor of this virus shows that researchers must think outside the box.

    • Catherine L. Murray
    •  & Charles M. Rice

  • Technology Feature |

    The scientific community now seems convinced that small RNAs will become therapies, if new tools can help these large molecules to make it safely into cells. Monya Baker reports.

    • Monya Baker

  • News Feature |

    After years of wrangling over the chemical's toxicity, researchers are charting a new way forwards. Brendan Borrell investigates how the debate has reshaped environmental-health studies.

    • Brendan Borrell

  • Letter |

    Almost 200 million people worldwide are chronically infected with hepatitis C virus. Current treatments are poorly tolerated and not wholly effective, so new drugs are needed. Here, a potent new inhibitor of hepatitis C virus is described. This inhibitor targets the viral protein NS5A, and shows potential as part of a therapeutic regimen based on a combination of viral inhibitors.

    • Min Gao
    • , Richard E. Nettles
    •  & Lawrence G. Hamann

  • Letter |

    Analogues of migrastatin — a natural product secreted by Streptomyces — are potent inhibitors of tumour cell migration and metastasis. Here, the underlying mechanism is elucidated: these migrastatin analogues target and inhibit the activity of the actin-bundling protein fascin. Hence proteins such as fascin might present new molecular targets for cancer treatments.

    • Lin Chen
    • , Shengyu Yang
    •  & Xin-Yun Huang

  • News & Views |

    The addition of a fatty acid to certain proteins is vital for the survival of protozoa that cause sleeping sickness and of their mammalian hosts. Compounds that target this process in the protozoa are now reported.

    • George A. M. Cross

  • News |

    'Legal high' set to become illegal despite resignation of crucial drugs adviser.

    • Daniel Cressey

  • Letter |

    It has previously been shown in mice and non-human primates that systemically delivered short RNA molecules can inhibit gene expression. Here it is shown that a short interfering RNA (siRNA) can be systemically delivered, using nanoparticles, to a solid tumour in humans. The siRNA mediates cleavage of its target mRNA, thereby also reducing levels of the encoded protein. This proof-of-principle study confirms the potential of this technology for treating human disease.

    • Mark E. Davis
    • , Jonathan E. Zuckerman
    •  & Antoni Ribas

  • News & Views |

    Inhibitors of RAF enzymes can suppress or activate the same signalling pathway. The details of how this happens provide a cautionary note for those targeting the pathway for anticancer drug discovery.

    • Karen Cichowski
    •  & Pasi A. Jänne

  • News |

    The drug stunts limb development in zebrafish and chicks by binding to a protein called cereblon.

    • Janet Fang

  • News & Views |

    Every machine is made of parts. But, as the new structure of the HIV integrase enzyme in complex with viral DNA shows, one could not have predicted from the individual parts just how this machine works.

    • Robert Craigie

  • Column |

    To sustain innovation, pharmaceutical companies will have to change the way they do research, says Derek Lowe. But does anyone know what changes to make?

    • Derek Lowe

  • News |

    Asia defies patent-filing downturn as global economy slips.

    • David Cyranoski

  • Article |

    Benzodiazepines, such as valium, are used both in clinics and for recreational purposes, but lead to addiction in some individuals. Addictive drugs increase the levels of dopamine and trigger synaptic adaptations in the mesolimbic reward system, but the neural basis for the addictive nature of benzodiazepines remains elusive. Here, they are shown to increase firing of dopamine neurons in the ventral tegmental area through GABAA receptor activation in nearby interneurons.

    • Kelly R. Tan
    • , Matthew Brown
    •  & Christian Lüscher

  • Article |

    To survive and evade host responses, malaria parasites export several hundred proteins into the host cell on infection. A feature of these proteins is a conserved, pentameric motif that is cleaved by an unknown protease before export. This is one of two independent studies revealing the identity of the protease as plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. This enzyme is essential for parasite viability and is an attractive candidate for drug development.

    • Justin A. Boddey
    • , Anthony N. Hodder
    •  & Alan F. Cowman

  • Letter |

    Heat shock protein 70 (Hsp70) is a molecular chaperone which, by inhibiting lysosomal membrane permeabilization, promotes the survival of stressed cells. Hsp70 is now shown to stabilize lysosomes by binding to an anionic phospholipid, BMP, resulting in stimulation of acid sphingomyelinase (ASM) activity. Notably, the decreased ASM activity and lysosomal stability seen in patients with Niemann–Pick disease can be corrected by treatment with recombinant Hsp70.

    • Thomas Kirkegaard
    • , Anke G. Roth
    •  & Marja Jäättelä

  • Brief Communications Arising |

    • Sophie Brinster
    • , Gilles Lamberet
    •  & Claire Poyart

  • Letter |

    High mutation rates in the influenza A virus facilitate the generation of viral escape mutants, rendering vaccines and drugs potentially ineffective, but targeting host cell determinants could prevent viral escape. Here, 287 human host cell genes influencing influenza A virus replication are found using a genome-wide RNA interference screen. An independent assay is then used to investigate overlap between genes necessary for different viral strains.

    • Alexander Karlas
    • , Nikolaus Machuy
    •  & Thomas F. Meyer

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