Chemical libraries

Chemical libraries are collections of molecules that are synthesized with the aim that they represent a given fraction of the theoretically possible chemical compounds that have yet been made. Research is focused on both the generation of libraries and on new methodology to screen them in the search for new or improved properties.

Latest Research and Reviews

  • Research | | open

    Investigation of a reaction scope usually starts with the optimization for a model substrate. Here, the authors apply a time-efficient multi-substrate screening approach to identify a general organocatalyst for the Diels–Alder reaction of cyclopentadiene with α,β-unsaturated aldehydes.

    • Hyejin Kim
    • , Gabriela Gerosa
    • , Jonas Aronow
    • , Pinar Kasaplar
    • , Jie Ouyang
    • , Julia B. Lingnau
    • , Paul Guerry
    • , Christophe Farès
    •  & Benjamin List
  • Research |

    Using a make-on-demand library that contains hundreds-of-millions of molecules, structure-based docking was used to identify compounds that, after synthesis and testing, are shown to interact with AmpC β-lactamase and the D4 dopamine receptor with high affinity.

    • Jiankun Lyu
    • , Sheng Wang
    • , Trent E. Balius
    • , Isha Singh
    • , Anat Levit
    • , Yurii S. Moroz
    • , Matthew J. O’Meara
    • , Tao Che
    • , Enkhjargal Algaa
    • , Kateryna Tolmachova
    • , Andrey A. Tolmachev
    • , Brian K. Shoichet
    • , Bryan L. Roth
    •  & John J. Irwin
    Nature 566, 224-229
  • Research |

    A combination of genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling enables the discovery of therapeutically targetable tumor dependencies in rare tumors.

    • Tanaz Sharifnia
    • , Mathias J. Wawer
    • , Ting Chen
    • , Qing-Yuan Huang
    • , Barbara A. Weir
    • , Ann Sizemore
    • , Matthew A. Lawlor
    • , Amy Goodale
    • , Glenn S. Cowley
    • , Francisca Vazquez
    • , Christopher J. Ott
    • , Joshua M. Francis
    • , Slim Sassi
    • , Patricia Cogswell
    • , Hadley E. Sheppard
    • , Tinghu Zhang
    • , Nathanael S. Gray
    • , Paul A. Clarke
    • , Julian Blagg
    • , Paul Workman
    • , Josh Sommer
    • , Francis Hornicek
    • , David E. Root
    • , William C. Hahn
    • , James E. Bradner
    • , Kwok K. Wong
    • , Paul A. Clemons
    • , Charles Y. Lin
    • , Joanne D. Kotz
    •  & Stuart L. Schreiber
    Nature Medicine 25, 292-300
  • Research | | open

    Preparation of xanthene-containing compounds has been limited due to structural bias existing methods pose. Here, the authors developed a mild, diversity-oriented method for rhodamines synthesis, leading to the finding of compounds with antibacterial potency against a variety of bacterial species.

    • Xiao Luo
    • , Liujia Qian
    • , Yansheng Xiao
    • , Yao Tang
    • , Yang Zhao
    • , Xia Wang
    • , Luyan Gu
    • , Zuhai Lei
    • , Jianming Bao
    • , Jiahui Wu
    • , Tingting He
    • , Fupin Hu
    • , Jing Zheng
    • , Honglin Li
    • , Weiping Zhu
    • , Lei Shao
    • , Xiaojing Dong
    • , Daijie Chen
    • , Xuhong Qian
    •  & Youjun Yang
  • Research |

    Rapamycin and FK506 are macrocycles that contain an FKBP-binding domain and an effector domain responsible for interacting with their respective targets, mTOR and calcineurin. Now, a 45,000-compound macrocycle library has been synthesized by fusing oligopeptides with synthetic FKBP-binding domains. Screening and subsequent optimization yielded a highly potent FKBP-dependent inhibitor of hENT1.

    • Zufeng Guo
    • , Sam Y. Hong
    • , Jingxin Wang
    • , Shahid Rehan
    • , Wukun Liu
    • , Hanjing Peng
    • , Manisha Das
    • , Wei Li
    • , Shridhar Bhat
    • , Brandon Peiffer
    • , Brett R. Ullman
    • , Chung-Ming Tse
    • , Zlatina Tarmakova
    • , Cordelia Schiene-Fischer
    • , Gunter Fischer
    • , Imogen Coe
    • , Ville O. Paavilainen
    • , Zhaoli Sun
    •  & Jun O. Liu

News and Comment

  • Editorial |

    Encoded chemical libraries can be used to screen a vast array of compounds against a protein target to identify potent binders. A collection of articles in this issue discuss different methods to increase the chemical space sampled by encoded macrocycle libraries and the advantages that such libraries offer for discovering new drug leads.

  • Comments and Opinion |

    Ghotas Evindar, Chemistry Group Leader at GlaxoSmithKline, talks with Nature Chemistry about the advantages of using encoded libraries in drug discovery and the challenges these technologies present.

    • Russell Johnson
    Nature Chemistry 10, 690-691
  • News and Views |

    Certain drug targets have been deemed undruggable because of the difficulty in finding pharmacologically useful inhibitors. Now, two teams have developed exciting technologies for the creation of diverse collections of macrocyclic molecules and have demonstrated their usefulness for discovering macrocyclic inhibitors.

    • Emil S. Iqbal
    •  & Matthew C. T. Hartman
    Nature Chemistry 10, 692-694
  • Comments and Opinion |

    To fully leverage the potential of human-induced pluripotent stem cells (hiPSCs), improved and standardized reprogramming methods and large-scale collections of hiPSC lines are needed, and the stem cell community must embrace chemical biology methodology for target identification and validation.

    • Andrei Ursu
    • , Hans R Schöler
    •  & Herbert Waldmann