[CAS NO. 2770300-35-9] KR-39038
PRODUCTS SPECIFICATIONS [2770300-35-9]
DESCRIPTION [2770300-35-9]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 475.00 |
| Molecular Formula | C24H32ClFN6O |
| SMILES | O=C1N=C(C2=C(Cl)C=CC=C2)NC3=CC(NCCCNCCCCNCCCN)=C(C=C13)F |
Summary
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 [1] .
IC50 & Target
|
HDAC5 |
In Vitro
KR-39038 (0-1.0 μM, 24 h) significantly inhibits angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell 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
[1]
.
Pharmacokinetic Parameters of KR-39038 in Sprague-Dawley rats
[1]
.
| 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) [1] |
| 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) [1] |
| 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 [1] |
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
Solvent & Solubility
DMSO : 115 mg/mL ( 242.11 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1053 mL | 10.5263 mL | 21.0526 mL |
| 5 mM | 0.4211 mL | 2.1053 mL | 4.2105 mL |
| 10 mM | 0.2105 mL | 1.0526 mL | 2.1053 mL |