KR-39038
目录号 : GC67883KR-39038 是一种口服有效的 GRK5 (G 蛋白偶联受体激酶 5) 抑制剂，IC50 为 0.02 μM。在新生儿心肌细胞中，KR-39038 通过抑制 HDAC5 通路，显著抑制血管紧张素 II 诱导的细胞肥大。KR-39038 具有明显的抗心肌肥厚作用和改善心功能。KR-39038 可用于心力衰竭的研究。
Cas No.:2770300-35-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
KR-39038 is an orally active and potent GRK5 (G protein-coupled receptor kinase 5) inhibitor, with an IC50 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].
KR-39038 (0-1.0 μM, 24 h) significantly inhibits angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes[1].
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. |
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) |
| Cmax (µg/mL) | NA | 5.2 ± 2.8 |
| Tmax (h) | NA | 0.7 ± 0.2 |
| t1/2 (h) | 0.7 ± 0.04 | 2.3 ± 2.9 |
| AUC0-∞ (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 |
| 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. |
[1]. Lee JH, et al. KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure. Biomol Ther (Seoul). 2020 Sep 1;28(5):482-489.
| Cas No. | 2770300-35-9 | SDF | Download SDF |
| 分子式 | C24H32ClFN6O | 分子量 | 475 |
| 溶解度 | DMSO : 115 mg/mL (242.11 mM; Need ultrasonic) | 储存条件 | 4°C, stored under nitrogen, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure
Biomol Ther (Seoul) 2020 Sep 1;28(5):482-489.PMID:32856617DOI:PMC7457178
G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl) amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC50 value=0.02 μM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/ day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.