A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors of Mycobacterium tuberculosis InhA

  • Alexander L. Perryman, Weixuan Yu, Xin Wang, Sean Ekins, Stefano Forli, Shao-Gang Li, Joel S. Freundlich, Peter J. Tonge, Arthur J. Olson
  • Journal of Chemical Information and Computer Sciences, March 2015, American Chemical Society (ACS)
  • DOI: 10.1021/ci500672v

Fragment-like inhibitors of InhA

What is it about?

A docking experiment using 5.6M molecules against M. tuberculosis InhA. Of these the NCI compounds (316000) were evaluated as it was free to obtain samples. 91 compounds were visually inspected,, 19 tested in the enzyme assay and 8 compounds inhibited the enzyme.

Why is it important?

This shows we can find fragment like leads in the NCI compounds which represents approx. 5% of all the compounds docked in the GO FAM experiment. The hits have low structural similarity to known InhA inhibitors.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

I was particularly interested to see how the hits compared to known InhA inhibitors using the compounds curated in TB Mobile. We made use of a PCA analysis and Tanimoto similarity.

Read Publication

http://dx.doi.org/10.1021/ci500672v

The following have contributed to this page: Dr Sean Ekins