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  • Poster presentation
  • Open Access

Design and development of novel non-peptide agonists at NPR-C

  • 1Email author,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 3 and
  • 1
BMC Pharmacology201111 (Suppl 1) :P54

  • Published:


  • Peptide
  • Molecular Modelling
  • Mesenteric Artery
  • Chemical Synthesis
  • Vascular Tone


Endothelium-derived C-type natriuretic peptide (CNP) possesses cytoprotective and anti-atherogenic functions that regulate vascular tone and smooth-muscle relaxation and might be key in protecting against ischaemia-reperfusion injury [1]. The finding that many of the vasoprotective effects of CNP are mediated by the natriuretic peptide receptor type-C (NPR-C) suggests that this receptor might represent a novel therapeutic target for the treatment of cardiovascular diseases. Thus, we have designed and developed small molecule drug-like mimetics of CNP agonists at NPRC.

Methods and results

We employ a multi-disciplinary approach that comprises molecular modelling, chemical synthesis and biological and functional assays. The crystal structure of NPR-C was used as the starting point for the design of peptidic and subsequently non-peptidic ligands to the receptor [2]. We have determined which fragments of CNP are crucial for binding to NPR-C and modified the NPR-C antagonist AP-811 using pharmacophore searches to replace the peptide component, which led to the design of a library of compounds that were subsequently synthesised, tested and optimised [3].


Novel and selective non-peptide NPR-C agonists have been identified that relax rat isolated mesenteric arteries in vitro. We foresee that such molecules will facilitate the development of potential therapeutic agents for cardiovascular diseases.

Authors’ Affiliations

Wolfson Institute for Biomedical Research, University College London, London, WC1E, 6BT, UK
Institute for Structural and Molecular Biology, University College London, London, WC1E, 6BT, UK
Neuroscience, Physiology & Pharmacology, University College London, London, WC1E, 6BT, UK


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© Quinteiro et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.