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

49 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

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

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