Skip NavigationSkip to Content
Return Return to Search Results

Identification of small molecule inhibitors of anthrax lethal factor

  1. Author:
    Panchal, R. G.
    Hermone, A. R.
    Nguyen, T. L.
    Wong, T. Y.
    Schwarzenbacher, R.
    Schmidt, J.
    Lane, D.
    McGrath, C.
    Turk, B. E.
    Burnett, J.
    Aman, M. J.
    Little, S.
    Sausville, E. A.
    Zaharevitz, D. W.
    Cantley, L. C.
    Liddington, R. C.
    Gussio, R.
    Bavari, S.

  2. Author Address

    Panchal, RG, NCI Frederick, Dev Therapeut Program, Frederick, MD 21702 USA NCI Frederick, Dev Therapeut Program, Frederick, MD 21702 USA. Burnham Inst, La Jolla, CA 92037 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
    1. Year: 2004
  2. Journal: Nature Structural & Molecular Biology
    1. 11
    2. 1
    3. Pages: 67-72
  4. Type of Article: Article
  1. Abstract:

    The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin composed of protective antigen (PA), lethal factor(LF) and edema factor (EF). LF is a Zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell death. We report here the identification of small molecule (nonpeptidic) inhibitors of LF. Using a two-stage screening assay, we determined the LF inhibitory properties of 19 compounds. Here, we describe six inhibitors on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository. Three of these compounds have K-i values in the 0.5-5 muM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel