KR-39038

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KR-39038

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

2770300-35-9

KR-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。

生物活性

KR-39038 is an orally active and potentGRK5(G protein-coupled receptor kinase 5) inhibitor, with anIC₅₀of 0.02 μM. KR-39038 significantly inhibits angiotensin II-induced cellular hypertrophy through suppression ofHDAC5pathway 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

体外研究
(In Vitro)

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.

体内研究
(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

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.

分子量

475.00

性状

Solid

Formula

C₂₄H₃₂ClFN₆O

CAS 号

2770300-35-9

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)

溶解性数据

In Vitro:

DMSO : 115 mg/mL(242.11 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

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

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℃, 6 months; -20℃, 1 month (stored under nitrogen, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。