Read the May issue

Including articles on illuminating the druggable genome, targeting inflammation in Alzheimer disease and kinases as drug targets

Latest Reviews

  • Review Article |

    Covalent modifications of RNA — mediated by RNA-modifying proteins (RMPs) — affect RNA stability and translation to proteins, and some of these RMPs have been implicated in cancer. Here, Copeland and colleagues review the current understanding of RNA modifications with a focus on mRNA methylation and assess the potential of RMPs as novel anticancer targets.

    • P. Ann Boriack-Sjodin
    • , Scott Ribich
    •  & Robert A. Copeland
  • Review Article |

    Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. This Review describes the progress made in recent years in inhibiting IL-6-signalling and analyses the advantages and disadvantages of these approaches.

    • Christoph Garbers
    • , Sylvia Heink
    • , Thomas Korn
    •  & Stefan Rose-John
  • Review Article |

    Prodrug strategies can be used to overcome pharmacokinetic and pharmacodynamic issues in many therapeutic agents. Here, Rautio and colleagues discuss which approaches have been most successful, particularly in the past 10 years, and highlight the challenges in incorporating prodrug moieties during drug development.

    • Jarkko Rautio
    • , Nicholas A. Meanwell
    • , Li Di
    •  & Michael J. Hageman
  • Review Article |

    Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article highlights how the design and synthesis of such libraries have been enabled by modern synthetic chemistry and illustrates the impact of the resultant chemical probes and drug leads in a wide range of diseases.

    • Christopher J. Gerry
    •  & Stuart L. Schreiber
  • Analysis |

    In 2014, the Illuminating the Druggable Genome programme was launched to promote the exploration of currently understudied but potentially druggable proteins. This article discusses how the systematic collection and processing of a wide array of biological and chemical data as part of this programme has enabled the development of evidence-based criteria for tracking the target development level of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. It also highlights the nature of the unexplored therapeutic opportunities for major protein families.

    • Tudor I. Oprea
    • , Cristian G. Bologa
    • , Søren Brunak
    • , Allen Campbell
    • , Gregory N. Gan
    • , Anna Gaulton
    • , Shawn M. Gomez
    • , Rajarshi Guha
    • , Anne Hersey
    • , Jayme Holmes
    • , Ajit Jadhav
    • , Lars Juhl Jensen
    • , Gary L. Johnson
    • , Anneli Karlson
    • , Andrew R. Leach
    • , Avi Ma'ayan
    • , Anna Malovannaya
    • , Subramani Mani
    • , Stephen L. Mathias
    • , Michael T. McManus
    • , Terrence F. Meehan
    • , Christian von Mering
    • , Daniel Muthas
    • , Dac-Trung Nguyen
    • , John P. Overington
    • , George Papadatos
    • , Jun Qin
    • , Christian Reich
    • , Bryan L. Roth
    • , Stephan C. Schürer
    • , Anton Simeonov
    • , Larry A. Sklar
    • , Noel Southall
    • , Susumu Tomita
    • , Ilinca Tudose
    • , Oleg Ursu
    • , Dušica Vidović
    • , Anna Waller
    • , David Westergaard
    • , Jeremy J. Yang
    •  & Gergely Zahoránszky-Köhalmi
  • Review Article |

    Existing kinase inhibitor drugs predominantly target receptor tyrosine kinases in cancer. Here, Gray and Ferguson review novel kinase targets in oncology, degenerative diseases, inflammatory disorders and infectious diseases. Advances in medicinal chemistry, selectivity profiling and computer-aided drug design, which are enabling the design of improved kinase inhibitors, are discussed.

    • Fleur M. Ferguson
    •  & Nathanael S. Gray

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