Cinaciguat hydrochloride

"目录号: HY-14181A

GPCR/G Protein-

Cinaciguat hydrochloride 是一种有效的可溶性鸟苷酸环化酶 (GC) 活化剂，在血小板中EC50值为 15 nM。

Guanylate Cyclase

生物活性

Description

Cinaciguat hydrochloride is a potent solubleguanylate cyclase(GC) activator withEC50of 15 nM in platelets.

IC50& Target

EC50:15 nM (Guanylate cyclase)[1]

In Vitro

In platelets, Cinaciguat (BAY 58-2667) is a potent GC activator (EC5015 nM) but the maximum effect is only about 1% of that achievable with NO. Concentration-response curves for Cinaciguat are constructed after 1 min exposure in the presence of sildenafil. Without ODQ, the EC50is 18 nM, and in the presence of ODQ the potency of Cinaciguat is not significantly different, the EC50being 13 nM. The potency of Cinaciguat in platelets (EC5015 nM) is very similar to estimates made on purified recombinant GC. Cinaciguat at a maximally effective concentration of 1 μM stimulates control GC activity to about 25% of that observed with NO and, contrasting with the stimulation by NO, this level of activity remained constant as the proportion of ODQ-pretreated GC is increased[1].

In Vivo

Administration of Cinaciguat decreased BP and increased HR in both apo-sGC mice and WT mice. In fact, the BP-lowering effect of Cinaciguat in apo-sGC mice is significantly greater and longer lasting than in WT mice. In addition, Cinaciguat decreased BP in apo-sGC mice at concentrations that did not affect BP in WT mice. Furthermore, the IC50values for Cinaciguat-induced ex vivorelaxation of precontracted aortas are threefold lower in apo-sGC mice than in WT mice (IC50=0.2 nM and 0.7 nM, respectively). Together, our results suggest that sGC activators like Cinaciguat but not sGC stimulators like BAY 41-2272 activate apo-sGC. In addition, the observation that Cinaciguat can modulate vasorelaxation and BP in WT mice suggests that even in healthy mice, a subset of the available sGC pool is haem-free and responsive to sGC activators[2].

Clinical Trial

NCT00559650

Bayer

Congestive Heart Failure

December 2007

Phase 2

NCT01067859

Bayer

Acute Heart Failure

March 2010

Phase 2

NCT01064037