Monday, September 5, 2011

Targeting Multiple Conformations Leads to Small Molecule Inhibitors of the uPAR•uPA Protein-Protein Interaction that Block Cancer Cell Invasion

The uPAR and uPA protein-protein interaction is known to have an effect in tumor formation and progression. This article is the first to discuss a small molecule that was found to inhibit uPAR:uPA interactions. The molecule (IPR-456) was found through a virtual screening of 80000 compounds. Due to the involvement of uPAR and uPA in metastasis, discovery of IPR-456 could lead to a greater understanding and possible prevention of cancer and other diseases.
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2 comments:

  1. CynthiaSeptember 9, 2011 at 4:19 PM

    I thought it was interesting that only one compound emerged from virtual screening of the crystal structure and the assay screening, to be active. Does that happen often? This just shows that predicting and solving protein-protein interaction with small molecules is very difficult!

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  2. AnonymousSeptember 15, 2011 at 5:02 PM

    I would say that is pretty good considering they only physically screened 50 compounds. I feel that you can get some good data from computers, but if they were really good at finding real inhibitors we wouldn't even try anything else.

    The one compound had a IC50 around 10uM, which is relatively high. Does anyone think that this paper could be enhanced by fragment based screening? They already have a hit and some structure information. I think this may be a good case for fragment based application.

    The molecules could easily target either side of the protein-protein interaction and may allow for multiple fragment hits.

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