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

Megumi Kawai*, Nwe Y. BaMaung, Steve D. Fidanze, Scott A. Erickson, Jason S. Tedrow, William J. Sanders, Anil Vasudevan, Chang Park, Charles Hutchins, Kenneth M. Comess, Douglas Kalvin, Jieyi Wang, Qian Zhang, Pingping Lou, Lora Tucker-Garcia, Jennifer Bouska, Randy L. Bell, Richard Lesniewski, Jack Henkin, George S. Sheppard

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    43 Scopus citations

    Abstract

    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 Mn2+ 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.

    Original languageEnglish (US)
    Pages (from-to)3574-3577
    Number of pages4
    JournalBioorganic and Medicinal Chemistry Letters
    Volume16
    Issue number13
    DOIs
    StatePublished - Jul 1 2006

    Keywords

    • Antiproliferative
    • MetAP2
    • Sulfonamide

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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