A new small molecule inhibitor of soluble guanylate cyclase

Bioorg Med Chem. 2015 Sep 1;23(17):5303-10. doi: 10.1016/j.bmc.2015.07.074. Epub 2015 Aug 4.

Abstract

Soluble guanylate cyclase (sGC) is a haem containing enzyme that regulates cardiovascular homeostasis and multiple mechanisms in the central and peripheral nervous system. Commonly used inhibitors of sGC activity act through oxidation of the haem moiety, however they also bind haemoglobin and this limits their bioavailability for in vivo studies. We have discovered a new class of small molecule inhibitors of sGC and have characterised a compound designated D12 (compound 10) which binds to the catalytic domain of the enzyme with a KD of 11 μM in a SPR assay.

Keywords: Nitric oxide; ODQ; Surface plasmon resonance; sGC (soluble guanylate cyclase).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Enzyme Activators / chemistry*
  • Enzyme Activators / pharmacology*
  • Guanylate Cyclase / antagonists & inhibitors*
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / metabolism
  • Humans
  • Molecular Docking Simulation
  • Nitric Oxide / metabolism
  • Quinoxalines / chemistry*
  • Quinoxalines / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Soluble Guanylyl Cyclase

Substances

  • Enzyme Activators
  • Quinoxalines
  • Receptors, Cytoplasmic and Nuclear
  • Small Molecule Libraries
  • Nitric Oxide
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase