A new small molecule inhibitor of soluble guanylate cyclase

作者:Mota Filipa; Gane Paul; Hampden Smith Kathryn; Allerston Charles K; Garthwaite John; Selwood David L*
来源:Bioorganic & Medicinal Chemistry, 2015, 23(17): 5303-5310.
DOI:10.1016/j.bmc.2015.07.074

摘要

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 K-D of 11 mu M in a SPR assay.

  • 出版日期2015-9-1