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. Author manuscript; available in PMC: 2008 Feb 3.
Published in final edited form as: Nat Rev Drug Discov. 2006 Sep;5(9):755–768. doi: 10.1038/nrd2038

Table 2. Main haem-independent activators of soluble guanylate cyclase.

Structure Name Comments Refs
graphic file with name nihms38124t6.jpg BAY 58–2667

  • Activity independent from the presence of haem

  • Activates haem-deficient/oxidized subpopulation of sGC, therefore has additive effect with NO

  • Stabilizes protein levels of oxidized/haem-free sGC that is prone to ubiquitin- mediated degradation

  • ∼37-fold activation of purified rat sGC (∼200-fold activation when this preparation is fully oxidized/haem-free)

  • EC50 for haem-free/oxidized sGC: ∼10 nM

  • Kd for oxidized sGC: ∼1 nM

  • No PDE inhibition at 10 μM

  • Increases maximal catalytic rate of sGC

  • IC50 for relaxation of rabbit saphenous artery: 0.4 nM

  • IC50 for relaxation of pig coronary artery: 0.5 nM

  • IC50 for relaxation of dog femoral vein: 3.6 nM

  • IC50 for U-46619-induced aggregation of washed human platelets: 0.05 μM (in platelet-rich plasma: 0.5 μM)

  • Causes a stronger relaxation of diseased blood vessels (from different animal models of cardiovascular diseases associated with oxidative stress) than of healthy blood vessels

 18,46, 70,80 83
graphic file with name nihms38124t7.jpg HMR-1766 (related derivative: S-3448)

  • Activity independent from the presence of haem

  • Activate haem-deficient/oxidized subpopulation of sGC, therefore have additive effect with NO

  • ∼50-fold activation of purified bovine sGC (∼90-fold activation when this preparation is fully oxidized)

  • EC50 for purified bovine sGC: 0.51 μM (HMR-1766) and 0.68 μM (S-3448)

  • IC50 for relaxation of rat thoracic aorta: 5.9 μM (S-3448); 1.2 μM and 0.4 μM (HMR-1766 without/with ODQ)

  • IC50 for relaxation of pig coronary artery: 1.2 μM (S-3448)

  • IC50 for relaxation of human corpus cavernosum: 10 μM (S-3448)

 82

CO, carbon monoxide; EC50, 50% effective concentration; IC50, 50% inhibitory concentration; Kd, equilibrium dissociation constant; NO, nitric oxide; PDE, phosphodiesterase; sGC, soluble guanylate cyclase.