2. Academic Validation
  3. Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor

Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor

  • Bioorg Med Chem Lett. 2014 Jun 1;24(11):2473-6. doi: 10.1016/j.bmcl.2014.04.013.
Kaitlin J Basham 1,  Vasudev R Bhonde 2,  Collin Kieffer 1,  James B C Mack 2,  Matthew Hess 2,  Bryan E Welm 3,  Ryan E Looper 4
Affiliations

Affiliations

  • 1 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
  • 2 Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
  • 3 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Surgery, University of Utah, Salt Lake City, UT 84112, USA.
  • 4 Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: [email protected].
PMID: 24767852 DOI: 10.1016/j.bmcl.2014.04.013
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.

Keywords

Aryl hydrocarbon receptor; Branching morphogenesis; Dioxin; Mammary gland; Oxadiazole.

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