IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v503y2013i7477d10.1038_nature12796.html
   My bibliography  Save this article

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

Author

Listed:
  • Jonathan M. Ostrem

    (Howard Hughes Medical Institute, University of California)

  • Ulf Peters

    (Howard Hughes Medical Institute, University of California)

  • Martin L. Sos

    (Howard Hughes Medical Institute, University of California)

  • James A. Wells

    (University of California)

  • Kevan M. Shokat

    (Howard Hughes Medical Institute, University of California)

Abstract

Small molecules are developed that irreversibly bind to the common G12C mutant of K-Ras but not the wild-type protein; crystallographic studies reveal the formation of an allosteric pocket that is not apparent in previous Ras studies, and the small molecules shift the affinity of K-Ras to favour GDP over GTP.

Suggested Citation

  • Jonathan M. Ostrem & Ulf Peters & Martin L. Sos & James A. Wells & Kevan M. Shokat, 2013. "K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions," Nature, Nature, vol. 503(7477), pages 548-551, November.
    • Handle: RePEc:nat:nature:v:503:y:2013:i:7477:d:10.1038_nature12796
    DOI: 10.1038/nature12796
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature12796
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature12796?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Katharine M. Wright & Sarah R. DiNapoli & Michelle S. Miller & P. Aitana Azurmendi & Xiaowei Zhao & Zhiheng Yu & Mayukh Chakrabarti & WuXian Shi & Jacqueline Douglass & Michael S. Hwang & Emily Han-Ch, 2023. "Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Kaja Kostyrko & Marta Román & Alex G. Lee & David R. Simpson & Phuong T. Dinh & Stanley G. Leung & Kieren D. Marini & Marcus R. Kelly & Joshua Broyde & Andrea Califano & Peter K. Jackson & E. Alejandr, 2023. "UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. James Schiemer & Andrew Maxwell & Reto Horst & Shenping Liu & Daniel P. Uccello & Kris Borzilleri & Nisha Rajamohan & Matthew F. Brown & Matthew F. Calabrese, 2023. "A covalent BTK ternary complex compatible with targeted protein degradation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Arafath K. Najumudeen & Sigrid K. Fey & Laura M. Millett & Catriona A. Ford & Kathryn Gilroy & Nuray Gunduz & Rachel A. Ridgway & Eve Anderson & Douglas Strathdee & William Clark & Colin Nixon & Jenni, 2024. "KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kai-Bo Wang & Yushuang Liu & Jinzhu Li & Chengmei Xiao & Yingying Wang & Wei Gu & Yipu Li & Yuan-Zheng Xia & Tingdong Yan & Ming-Hua Yang & Ling-Yi Kong, 2022. "Structural insight into the bulge-containing KRAS oncogene promoter G-quadruplex bound to berberine and coptisine," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:503:y:2013:i:7477:d:10.1038_nature12796. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.