Chemical tools

Chemical tools are small molecules used as probes of a chemical or biological process. Studying the effects of chemical tools on a system can lead to new insight into the molecular target of the small molecule and the pathways it acts in. Chemical probes with defined targets can be attractive as drugs in clinical pharmacology.

Featured

Latest Research and Reviews

  • Research |

    MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance analysis.

    • Rebecca C. Coll
    • , James R. Hill
    • , Christopher J. Day
    • , Alina Zamoshnikova
    • , Dave Boucher
    • , Nicholas L. Massey
    • , Jessica L. Chitty
    • , James A. Fraser
    • , Michael P. Jennings
    • , Avril A. B. Robertson
    •  & Kate Schroder
  • Research |

    A bioluminescent glucose-uptake probe enables accurate, real-time, non-invasive longitudinal imaging of d-glucose absorption both in vitro and in vivo.

    • Tamara Maric
    • , Georgy Mikhaylov
    • , Pavlo Khodakivskyi
    • , Arkadiy Bazhin
    • , Riccardo Sinisi
    • , Nicolas Bonhoure
    • , Aleksey Yevtodiyenko
    • , Anthony Jones
    • , Vishaka Muhunthan
    • , Gihad Abdelhady
    • , David Shackelford
    •  & Elena Goun
  • Research | | open

    Ceramides are lipids that act directly on mitochondria to trigger apoptosis, but the underlying mechanism remains largely unclear. Here authors use a photoactivatable ceramide probe combined with a computation approach and functional studies to identify the voltage-dependent anion channel VDAC2 as a direct effector of ceramide-mediated cell death.

    • Shashank Dadsena
    • , Svenja Bockelmann
    • , John G. M. Mina
    • , Dina G. Hassan
    • , Sergei Korneev
    • , Guilherme Razzera
    • , Helene Jahn
    • , Patrick Niekamp
    • , Dagmar Müller
    • , Markus Schneider
    • , Fikadu G. Tafesse
    • , Siewert J. Marrink
    • , Manuel N. Melo
    •  & Joost C. M. Holthuis
  • Reviews |

    Biochemical and cellular assays are often plagued by false positive readouts elicited by nuisance compounds. A significant proportion of those compounds are aggregators. This Review discusses the basis for colloidal aggregation, experimental methods for detecting aggregates and analyses recent progress in computer-based systems for detecting colloidal aggregation with particular emphasis on machine learning [In the online version of this Review originally published, the graphical abstract image was incorrectly credited to ‘Reven T.C. Wurman / Alamy Stock Photo’ this has now been corrected].

    Oleksii Telnov / Alamy Stock Photo

    • Daniel Reker
    • , Gonçalo J. L. Bernardes
    •  & Tiago Rodrigues
    Nature Chemistry 11, 402-418

News and Comment

  • News |

    Bioluminescence lights her way to measure glucose uptake in vivo, and why a chemist travels outside her comfort zone.

    • Vivien Marx
  • News and Views |

    The NLRP3 inflammasome contributes to pathogenic inflammation in a broad range of diseases, making it a highly relevant drug target. Two studies published in this issue found an inhibitor of NLRP3 inflammasome activation to directly bind NLRP3 within its central NACHT domain, interfering with ATP hydrolysis and structural changes critical for NLRP3 oligomerization and subsequent inflammasome formation.

    • Oliver Gorka
    • , Emilia Neuwirt
    •  & Olaf Groß
  • News and Views |

    Chemical probes that irreversibly inhibit protein function may be used across species to discover proteins. Combining phenotypic screening and activity-based protein profiling, a new study uncovers a discrete lipid signaling pathway regulating lifespan in the worm Caenorhabditis elegans.

    • Jürg Gertsch
  • News and Views |

    Powerful combinatorial peptide library methods allow the discovery of peptide leads from diverse libraries. A new platform based on tandem mass spectrometry peptide sequencing coupled with high-performance size-exclusion chromatography enables identification of high-affinity peptidic ligands from focused libraries.

    • Kit S. Lam