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Bioorg Med Chem Lett. 2006 Jul 1;16(13):3574-7. Epub 2006 May 2.

Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.

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  • 1Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.


We have screened molecules for inhibition of MetAP2 as a novel approach toward antiangiogenesis and anticancer therapy using affinity selection/mass spectrometry (ASMS) employing MetAP2 loaded with Mn(2+) as the active site metal. After a series of anthranilic acid sulfonamides with micromolar affinities was identified, chemistry efforts were initiated. The micromolar hits were quickly improved to potent nanomolar inhibitors by chemical modifications guided by insights from X-ray crystallography.

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