Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Feb 18;117(7):3363-3364.
doi: 10.1073/pnas.1918164117. Epub 2020 Feb 11.

The small molecule BI-2852 induces a nonfunctional dimer of KRAS

Timothy H Tran  1 , Patrick Alexander  1 , Srisathiyanarayanan Dharmaiah  1 , Constance Agamasu  1 , Dwight V Nissley  1 , Frank McCormick  1   2 , Dominic Esposito  1 , Dhirendra K Simanshu  1 , Andrew G Stephen  1 , Trent E Balius  3
Affiliations
Comment

The small molecule BI-2852 induces a nonfunctional dimer of KRAS

Timothy H Tran et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interest statement: F.M. is a consultant for the following companies: AduroBiotech; Amgen; Daiichi, Ltd.; PellePharm; Pfizer, Inc.; PMV Pharma; and Portola Pharmaceuticals. F.M. is Scientific Director of the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc. F.M. is a consultant for and cofounder of the following companies: Avidity, BridgeBio, KGen, and Quartz.

Figures

Fig. 1.
Fig. 1.
Dimer of KRAS with BI-2852. (A) Cartoon of BI-2852 KRAS dimer. Lig1 (cyan) and Lig2 (magenta) interact with both Ras1 (beige) and Ras2 (orange). (B) KRAS (ribbons) and key side chains are shown. (C) Zoom-in of the binding site: salt–bridge interactions shown (dashed lines). (D) Lid (green) and Basin (purple) are indicated on Ras1. Both Lig1 and Lig2 are shown on Ras1. The indole rings, colored green and purple, engage the Lid and Basin, respectively. (E) Absorbance A280 plotted as a function of elution volume: KRAS G12D-GppNHp with BI-2852 (orange) and apo KRAS G12D-GppNHp (blue).
See this image and copyright information in PMC

Comment in

  • Reply to Tran et al.: Dimeric KRAS protein-protein interaction stabilizers.
    Kessler D, Gollner A, Gmachl M, Mantoulidis A, Martin LJ, Zoephel A, Mayer M, Covini D, Fischer S, Gerstberger T, Gmaschitz T, Goodwin C, Greb P, Häring D, Hela W, Hoffmann J, Karolyi-Oezguer J, Knesl P, Kornigg S, Koegl M, Kousek R, Lamarre L, Moser F, Munico-Martinez S, Peinsipp C, Phan J, Rinnenthal J, Sai J, Salamon C, Scherbantin Y, Schipany K, Schnitzer R, Schrenk A, Sharps B, Siszler G, Sun Q, Waterson A, Wolkerstorfer B, Zeeb M, Pearson M, Fesik SW, McConnell DB. Kessler D, et al. Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3365-3367. doi: 10.1073/pnas.1921236117. Epub 2020 Feb 11. Proc Natl Acad Sci U S A. 2020. PMID: 32047042 Free PMC article. No abstract available.

Comment on

  • Drugging an undruggable pocket on KRAS.
    Kessler D, Gmachl M, Mantoulidis A, Martin LJ, Zoephel A, Mayer M, Gollner A, Covini D, Fischer S, Gerstberger T, Gmaschitz T, Goodwin C, Greb P, Häring D, Hela W, Hoffmann J, Karolyi-Oezguer J, Knesl P, Kornigg S, Koegl M, Kousek R, Lamarre L, Moser F, Munico-Martinez S, Peinsipp C, Phan J, Rinnenthal J, Sai J, Salamon C, Scherbantin Y, Schipany K, Schnitzer R, Schrenk A, Sharps B, Siszler G, Sun Q, Waterson A, Wolkerstorfer B, Zeeb M, Pearson M, Fesik SW, McConnell DB. Kessler D, et al. Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):15823-15829. doi: 10.1073/pnas.1904529116. Epub 2019 Jul 22. Proc Natl Acad Sci U S A. 2019. PMID: 31332011 Free PMC article.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kessler D., et al. , Drugging an undruggable pocket on KRAS. Proc. Natl. Acad. Sci. U.S.A. 116, 15823–15829 (2019). - PMC - PubMed
    1. Tran T. H., et al. , Data from “SI. The small molecule BI-2852 induces a non-functional dimer of KRAS.” Figshare. 10.6084/m9.figshare.11425995. Deposited 30 December 2019. - DOI - PubMed

Substances

LinkOut - more resources