Non-covalent triazole-based inhibitors of the SARS main proteinase 3CLpro

In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010.
[updated ].


ML300 (CID 46861530) is being declared as a new first in class 3CLpro probe inhibitor. ML300 belongs to a new series of triazole-based SARS main proteinase 3CLpro inhibitors that follow our first dipeptide probe ML188. Based upon X-ray crystal data from a related inhibitor, ML300 is believed to interact within the 3CLpro enzyme active site via a novel binding mode distinct from both our first probe ML188 and other known peptidomimetic inhibitors. Relative to ML188 and based upon X-ray crystal data, the MW of the triazole series described here can be reduced resulting in truncation to a single backbone amide. Structure-activity relationships taking into account ligand efficiency and studies leading to the identification of ML300 will be described. ML300 should allow others in the field to access a novel non-covalent starting point for 3CLpro inhibitor design and optimization.

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