KR-39038 is an orally active and potent GRK5 (G protein-coupled receptor kinase 5) inhibitor, with an IC 50 of 0.02 μM. KR-39038 significantly inhibits angiotensin II-induced cellular hypertrophy through suppression of HDAC5 pathway in neonatal cardiomyocytes. KR-39038 shows profound anti-hypertrophic effects and improved cardiac function. KR-39038 can be used for heart failure research
In Vitro
KR-39038 (0-1.0 μM, 24 h) significantly inhibits angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: Primary neonatal cardiomyocytes (isolated from S.D. rats (1-2 days old) using primary myocardial cell isolation kit) Concentration: 0 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1.0 μM Incubation Time: 24 h Result: Significantly inhibited angiotensin II-induced cellular hypertrophy at a concentration of 0.1 µM and higher concentrations. Decreased angiotensin II-induced HDAC5 phosphorylation at 0.3 µM and higher concentrations.
In Vivo
KR-39038 (0-30 mg/kg, Orally, once daily for 14 days) effectively attenuates both cardiac hypertrophy and dysfunction in experimental heart failure . Pharmacokinetic Parameters of KR-39038 in Sprague-Dawley rats . Parameters IV (5 mg/kg) PO (300 mg/kg) C max (µg/mL) NA 5.2 ± 2.8 T max (h) NA 0.7 ± 0.2 t 1/2 (h) 0.7 ± 0.04 2.3 ± 2.9 AUC 0-∞ (µg*h/mL) 3.4 ± 1.0 8.9 ± 5.0 CL (L/h/kg) 1.6 ± 0.5 NA Vss (L/kg) 1.2 ± 0.2 NA F (%) 4.3 ± 2.4 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: C57BL/6 mice (male, 20-24 g, transverse aortic constriction) Dosage: 30 mg/kg Administration: Orally, once a day for 2 weeks, starting from 24 h after the operation Result: Showed a 43% reduction in the left ventricular weight, and significantly attenuated the development of cardiac hypertrophy. Animal Model: Sprague-Dawley (S.D.) rats (male, 380-420 g, coronary artery ligation) Dosage: 10 mg/kg, 30 mg/kg Administration: Orally, once a day for 12 weeks, starting from 24 h after surgery Result: Showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. Animal Model: Sprague-Dawley (S.D.) rats Dosage: 5 mg/kg (IV), 300 mg/kg (Orally) Administration: IV or Orally, single (Pharmacokinetic Analysis) Result: The AUC ∞ values after intravenous injection with 10 mg/kg and oral administration of 300 mg/kg of KR-39038 were 3.4 ± 1.0 and 8.9 ± 5.0 µg·h/mL, respectively, resulting in 4.3% bioavailability.
