Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor

Kaitlin J. Basham, Vasudev R. Bhonde, Collin Kieffer, James B.C. Mack, Matthew Hess, Bryan E. Welm, Ryan E. Looper

Research output: Contribution to journalArticlepeer-review

Abstract

Bis-aryloxadiazoles are common scaffolds in medicinal chemistry due to their wide range of biological activities. Previously, we identified a 1,2,4-bis-aryloxadiazole that blocks mammary branching morphogenesis through activation of the aryl hydrocarbon receptor (AHR). In addition to defects in mammary differentiation, AHR stimulation induces toxicity in many other tissues. We performed a structure activity relationship (SAR) study of 1,2,4-bis-aryloxadiazole to determine which moieties of the molecule are critical for AHR activation. We validated our results with a functional biological assay, using desmosome formation during mammary morphogenesis to indicate AHR activity. These findings will aid the design of oxadiazole derivative therapeutics with reduced off-target toxicity profiles.

Original languageEnglish (US)
Pages (from-to)2473-2476
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2014
Externally publishedYes

Keywords

  • Aryl hydrocarbon receptor
  • Branching morphogenesis
  • Dioxin
  • Mammary gland
  • Oxadiazole

ASJC Scopus subject areas

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

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