A new small molecule inhibitor of soluble guanylate cyclase.
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.
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Filipa
F
Mota
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Paul
P
Gane
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Kathryn
K
Hampden-Smith
Structural Genomics Consortium, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
Charles K
CK
Allerston
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
John
J
Garthwaite
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom. Electronic address: d.selwood@ucl.ac.uk.
David L
DL
Selwood
D020134:Catalytic Domain; D020536:Enzyme Activators / Q000737:chemistry* / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009569:Nitric Oxide / Q000378:metabolism; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D000071756:Soluble Guanylyl Cyclase
D020536:Enzyme Activators; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; D054852:Small Molecule Libraries; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
Nitric oxide; ODQ; Surface plasmon resonance; sGC (soluble guanylate cyclase)