BAY-747 (C09-1112-961)

BAY-747 is an orally active and brain-penetrant stimulator of soluble guanylate cyclase ( sGC ). BAY-747 reverses L-NAME induced memory impairments and enhances cognition of rats in the object location task (OLT). BAY-747 also decreases blood pressure in both conscious normotensive and spontaneously hypertensive rats (SHR). BAY-747 improves function of the skeletal muscle associated with Duchenne muscular dystrophy (DMD) in mdx/mTRG2 mice modelIn VitroBAY-747 (100 nM) enhances AMPA receptor dynamics in an ex vivo acquisition-like cLTP model, in combination with WS. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: ex vivo acquisition-like cLTP model Concentration: 100 nM Incubation Time: Result: Increased the phosphorylation levels of S845 on GluA1.In VivoBAY-747 shows a brain to plasma ratio of 0.6 ± 2.0 at the investigated time frame, reflecting a relatively high brain penetration of 60% . BAY-747 (0.03-1.0 mg/kg,2 mL/kg ; po; 30 min before T1 in a 24 h interval OLT) enhance long-term memory acquisition processes in rat object location task (OLT) model, and also attenuates L-NAME induced short-term memory impairments. BAY-747 does not affect GluA1-containing AMPAR dynamics in the hippocampus . BAY-747 (0.003-0.3 mg/kg; po; single dose) decreases blood pressure in rats, and also (3 mg/kg; po; once daily for 35 days) increases body weight of rats in l-NAME-Treated Renin Transgenic model. BAY-747 (150 mg/kg of food; po; 16 weeks) improves grip strength and running speed in male mdx/mTRG2 mice, suggesting improved skeletal muscle function. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Rat object location task (OLT) model Dosage: 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg Administration: PO; 30 min before T1 in a 24 h interval OLT Result: Resulted significantly higher long-term memory performance at 0.03, 0.1, 0.3 and 1.0 mg/kg dose, 30 min before T1. Attenuated L-NAME induced short-term memory impairments at 0.3 mg/kg and 1 mg/kg. Did not enhance GluA1 trafficking at 1 mg/kg 24 h after treatment. Animal Model: Anesthetized, conscious spontaneously hypertensive and conscious normotensive ratsDosage: 0 mg/kg, 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, and 0.3 mg/kg Administration: IV; single dose Result: Produced a dose-dependent and long-lasting decrease in blood pressure in rats. Animal Model: l-NAME-Treated Renin Transgenic RatsDosage: 0.3 mg/kg, 3 mg/kg Administration: PO; once daily for 35 days; l-NAME treatment: 30 mg/kg, po, for 6 days Result: Resulted a significant weight gain among rats. Led to a dose-dependent increase of plasma cGMP. Decreased blood pressure only at 3 mg/kg.IC50& Target:Soluble guanylate cyclase (sGC). Molecular Formula: C22H26F2N4O2 Molecular Weight: 416.46