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Updated: Aug 2, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Identification of alkylidene hydrazides as glucagon receptor antagonists
1Department of Medicinal Chemistry, Pfizer Global Research and Development, La Jolla/Agouron Pharmaceuticals, Inc., San Diego, CA 92121, USA. anthony.ling@agouron.com
Abstract:
High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.
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